bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of LKB1-NUAK1 signalling enhances NF-κB activity in a spheroid model of high-grade serous ovarian cancer
Authors: Buensuceso Adrian , Fritz Jamie Lee , Collins Olga , Valdés Yudith Ramos , Borrelli Matthew J. , DiMattia Gabriel E. , Shepherd Trevor G. 
Published: February 2022

AbstractHigh-grade serous ovarian cancer (HGSOC) is an aggressive malignancy often diagnosed at an advanced stage. Although most HGSOC patients respond initially to debulking surgery combined with cytotoxic chemotherapy, many ultimately relapse with platinum-resistant disease. Thus, improving outcomes requires new ways of limiting metastasis and eradicating residual disease. We identified previously that Liver kinase B1 (LKB1) and its substrate NUAK1 are implicated in EOC spheroid cell viability and are required for efficient metastasis in orthotopic mouse models. Here, we sought to identify additional signalling pathways altered in EOC cells due to LKB1 or NUAK1 loss-of-function. Transcriptome analysis revealed that inflammatory signalling mediated by NF-κB transcription factors is hyperactive due to LKB1-NUAK1 loss in HGSOC cells and spheroids. Upregulated NF-κB signalling due to NUAK1 loss suppresses reactive oxygen species (ROS) production and sustains cell survival in spheroids. NF-κB signalling is also activated in HGSOC precursor fallopian tube secretory epithelial cell spheroids, and is further enhanced by NUAK1 loss. Finally, immunohistochemical analysis of OVCAR8 xenograft tumors lacking NUAK1 displayed increased RelB expression and nuclear staining. Our results support the idea that NUAK1 and NF-κB signalling pathways together regulate ROS and inflammatory signalling, supporting cell survival during each step of HGSOC pathogenesis. We propose that their combined inhibition may be efficacious as a novel therapeutic strategy for advanced HGSOC.
The sterility, stability and efficacy of repackaged ziv-aflibercept for intravitreal administration
Authors: Juhong Jakkrit , Pongsachareonnont Pear Ferreira , Somkijrungroj Thanapong , Mavichak Apivat , Varadisai Adisai , Chariyavilaskul Pajaree , Chatsuwan Tanittha , Suttichet Thitima Benjachat , Kulvichit Kittisak 
Published: February 2022

AbstractTo evaluate the sterility, stability, and efficacy of repackaged ziv-aflibercept in 1-mL plastic tuberculin syringes for intravitreal injection after storage for up to 90 days at controlled (4 °C) and ambient (25.8 °C) temperature. A total of 168 tuberculin-type 1-mL syringes were prepared containing ziv-aflibercept (100 mg/4 mL). Samples were stored at 4 °C and 25.8 °C for 0, 3, 7, 14, 21, 28, 60, and 90 days. At each time point, four samples were evaluated for the stability and binding affinity of anti-VEGF to VEGF (efficacy) using enzyme-linked immunosorbent assays (ELISAs). All samples were analyzed for microbial growth. No microbial growth was obtained from any of the ziv-aflibercept samples during each time point, indicating that the repackaged ziv-aflibercept stored at 4 °C and 25.8 °C remained sterile. ELISA analysis revealed no significant decrease in concentration, and binding affinity was observed, indicating that the stability and efficacy were preserved. However, the concentration of ziv-aflibercept decreased less than the minimum expected concentration of 8 ng/mL after 60 days at 4 °C and after 30 days at 25.8 °C. The repackaged anti-VEGF drug ziv-aflibercept does not lose stability or efficacy and remains uncontaminated if prepared under sterile conditions and stored at 4 °C for up to 60 days or stored at 25.8 °C for up to 30 days.
Prediction of nickel concentration in peri-urban and urban soils using hybridized empirical bayesian kriging and support vector machine regression
Authors: Agyeman Prince Chapman , Kebonye Ndiye Michael , John Kingsley , Borůvka Luboš , Vašát Radim , Fajemisim Olufadekemi 
Published: February 2022

AbstractSoil pollution is a big issue caused by anthropogenic activities. The spatial distribution of potentially toxic elements (PTEs) varies in most urban and peri-urban areas. As a result, spatially predicting the PTEs content in such soil is difficult. A total number of 115 samples were obtained from Frydek Mistek in the Czech Republic. Calcium (Ca), magnesium (Mg), potassium (K), and nickel (Ni) concentrations were determined using Inductively Coupled Plasma Optical Emission Spectroscopy. The response variable was Ni, while the predictors were Ca, Mg, and K. The correlation matrix between the response variable and the predictors revealed a satisfactory correlation between the elements. The prediction results indicated that support vector machine regression (SVMR) performed well, although its estimated root mean square error (RMSE) (235.974 mg/kg) and mean absolute error (MAE) (166.946 mg/kg) were higher when compared with the other methods applied. The hybridized model of empirical bayesian kriging-multiple linear regression (EBK-MLR) performed poorly, as evidenced by a coefficient of determination value of less than 0.1. The empirical bayesian kriging-support vector machine regression (EBK-SVMR) model was the optimal model, with low RMSE (95.479 mg/kg) and MAE (77.368 mg/kg) values and a high coefficient of determination (R2 = 0.637). EBK-SVMR modelling technique output was visualized using a self-organizing map. The clustered neurons of the hybridized model CakMg-EBK-SVMR component plane showed a diverse colour pattern predicting the concentration of Ni in the urban and peri-urban soil. The results proved that combining EBK and SVMR is an effective technique for predicting Ni concentrations in urban and peri-urban soil.
Hypsometric changes in urban areas resulting from multiple years of mining activity
Authors: Solarski Maksymilian , Machowski Robert , Rzetala Mariusz , Rzetala Martyna A. 
Published: February 2022

AbstractThe impact of multiple years of underground mining of minerals on changes in the elevation of an urban area has been evaluated using the case study of Bytom in southern Poland. Between 1883 and 2011, that city experienced changes in absolute minimum (from 250.0 to 243.0 m a.s.l.) and maximum (from 340.0 to 348.4 m a.s.l.) elevations. During that period, the difference between minimum and maximum elevations increased from 90.0 to 105.4 m. The consequence of underground mining has been the formation of extensive subsidence basins with a maximum depth of 35 m. Where the terrain became raised, its elevation rose most commonly by 1.1 m to 5.0 m, with maximum increase in elevation caused by human activity amounting to 35 m. The rate of anthropogenic subsidence in the city between 1883 and 2011 averaged 43 mm/year (5.5 m over the study period).
Collective patterns and stable misunderstandings in networks striving for consensus without a common value system
Authors: Falk Johannes , Eichler Edwin , Windt Katja , Hütt Marc-Thorsten 
Published: February 2022

AbstractCollective phenomena in systems of interacting agents have helped us understand diverse social, ecological and biological observations. The corresponding explanations are challenged by incorrect information processing. In particular, the models typically assume a shared understanding of signals or a common truth or value system, i.e., an agreement of whether the measurement or perception of information is ‘right’ or ‘wrong’. It is an open question whether a collective consensus can emerge without these conditions. Here we introduce a model of interacting agents that strive for consensus, however, each with only a subjective perception of the world. Our communication model does not presuppose a definition of right or wrong and the actors can hence not distinguish between correct and incorrect observations. Depending on a single parameter that governs how responsive the agents are to changing their world-view we observe a transition between an unordered phase of individuals that are not able to communicate with each other and a phase of an emerging shared signalling framework. We find that there are two types of convention-aligned clusters: one, where all social actors in the cluster have the same set of conventions, and one, where neighbouring actors have different but compatible conventions (‘stable misunderstandings’).
Urban–rural prostate cancer disparities in a regional state of Australia
Authors: Foley Georgea R. , Blizzard C. Leigh , Stokes Brian , Skala Marketa , Redwig Frank , Dickinson Joanne L. , FitzGerald Liesel M. 
Published: February 2022

AbstractMen living in regional and remote areas experience disparities in prostate cancer (PrCa) diagnosis, clinical characteristics and treatment modalities. We sought to determine whether such disparities exist in PrCa patients from Tasmania; a regional state of Australia with the second-highest rate of diagnosis and where over a third of residents live in outer regional and remote areas. Our study included clinicopathological data from 1526 patients enrolled in the Prostate Cancer Outcomes Registry-Tasmania. Regression analyses were undertaken to determine whether demographic, clinical and treatment variables differed between inner regional and outer regional/remote patients. Men from outer regional/remote areas were significantly more likely to reside in lower socio-economic areas, be diagnosed at a later age and with more clinically aggressive features. However, in contrast to previous studies, there were no overall differences in diagnostic or treatment method, although men from outer regional/remote areas took longer to commence active treatment and travelled further to do so. This study is the first to investigate PrCa disparities in a wholly regional Australian state and highlights the need to develop systematic interventions at the patient and healthcare level to improve outcomes in outer regional and remote populations in Australia and across the globe.
Altered TGFB1 regulated pathways promote accelerated tendon healing in the superhealer MRL/MpJ mouse
Authors: Kallenbach Jacob G. , Freeberg Margaret A. T. , Abplanalp David , Alenchery Rahul G. , Ajalik Raquel E. , Muscat Samantha , Myers Jacquelyn A. , Ashton John M. , Loiselle Alayna , Buckley Mark R. , van Wijnen Andre J. , Awad Hani A. 
Published: February 2022

AbstractTo better understand the molecular mechanisms of tendon healing, we investigated the Murphy Roth’s Large (MRL) mouse, which is considered a model of mammalian tissue regeneration. We show that compared to C57Bl/6J (C57) mice, injured MRL tendons have reduced fibrotic adhesions and cellular proliferation, with accelerated improvements in biomechanical properties. RNA-seq analysis revealed that differentially expressed genes in the C57 healing tendon at 7 days post injury were functionally linked to fibrosis, immune system signaling and extracellular matrix (ECM) organization, while the differentially expressed genes in the MRL injured tendon were dominated by cell cycle pathways. These gene expression changes were associated with increased α-SMA+ myofibroblast and F4/80+ macrophage activation and abundant BCL-2 expression in the C57 injured tendons. Transcriptional analysis of upstream regulators using Ingenuity Pathway Analysis showed positive enrichment of TGFB1 in both C57 and MRL healing tendons, but with different downstream transcriptional effects. MRL tendons exhibited of cell cycle regulatory genes, with negative enrichment of the cell senescence-related regulators, compared to the positively-enriched inflammatory and fibrotic (ECM organization) pathways in the C57 tendons. Serum cytokine analysis revealed decreased levels of circulating senescence-associated circulatory proteins in response to injury in the MRL mice compared to the C57 mice. These data collectively demonstrate altered TGFB1 regulated inflammatory, fibrosis, and cell cycle pathways in flexor tendon repair in MRL mice, and could give cues to improved tendon healing.
Hypertonic lactate for the treatment of intracranial hypertension in patients with acute brain injury
Authors: Bernini Adriano , Miroz John-Paul , Abed-Maillard Samia , Favre Eva , Iaquaniello Carolina , Ben-Hamouda Nawfel , Oddo Mauro 
Published: February 2022

AbstractHypertonic lactate (HL) is emerging as alternative treatment of intracranial hypertension following acute brain injury (ABI), but comparative studies are limited. Here, we examined the effectiveness of HL on main cerebral and systemic physiologic variables, and further compared it to that of standard hypertonic saline (HS). Retrospective cohort analysis of ABI subjects who received sequential osmotherapy with 7.5% HS followed by HL—given at equi-osmolar (2400 mOsmol/L) and isovolumic (1.5 mL/kg) bolus doses—to reduce sustained elevations of ICP (> 20 mmHg). The effect of HL on brain (intracranial pressure [ICP], brain tissue PO2 [PbtO2], cerebral microdialysis [CMD] glucose and lactate/pyruvate ratio [LPR]) and blood (chloride, pH) variables was examined at different time-points (30, 60, 90, 120 min vs. baseline), and compared to that of HS. A total of 34 treatments among 17 consecutive subjects (13 traumatic brain injury [TBI], 4 non-TBI) were studied. Both agents significantly reduced ICP (p < 0.001, at all time-points tested): when comparing treatment effectiveness, absolute ICP decrease in mmHg and the duration of treatment effect (median time with ICP < 20 mmHg following osmotherapy 183 [108–257] vs. 150 [111–419] min) did not differ significantly between HL and HS (all p > 0.2). None of the treatment had statistically significant effects on PbtO2 and CMD biomarkers. Treatment with HL did not cause hyperchloremia and resulted in a more favourable systemic chloride balance than HS (Δ blood chloride − 1 ± 2.5 vs. + 4 ± 3 mmol/L; p < 0.001). This is the first clinical study showing that HL has comparative effectiveness than HS for the treatment of intracranial hypertension, while at the same time avoiding hyperchloremic acidosis. Both agents had no significant effect on cerebral oxygenation and metabolism.
Hemojuvelin deficiency promotes liver mitochondrial dysfunction and predisposes mice to hepatocellular carcinoma
Authors: Allameh Abdolamir , Hüttmann Nico , Charlebois Edouard , Katsarou Angeliki , Gu Wen , Gkouvatsos Konstantinos , Pasini Elisa , Bhat Mamatha , Minic Zoran , Berezovski Maxim , Guido Maria , Fillebeen Carine , Pantopoulos Kostas 
Published: February 2022

AbstractHemojuvelin (HJV) enhances signaling to the iron hormone hepcidin and its deficiency causes iron overload, a risk factor for hepatocellular carcinoma (HCC). We utilized Hjv−/− mice to dissect mechanisms for hepatocarcinogenesis. We show that suboptimal treatment with diethylnitrosamine (DEN) triggers HCC only in Hjv−/− but not wt mice. Liver proteomics data were obtained by mass spectrometry. Hierarchical clustering analysis revealed that Hjv deficiency and DEN elicit similar liver proteomic responses, including induction of mitochondrial proteins. Dietary iron overload of wt mice does not recapitulate the liver proteomic phenotype of Hjv−/− animals, which is only partially corrected by iron depletion. Consistent with these data, primary Hjv−/− hepatocytes exhibit mitochondrial hyperactivity, while aged Hjv−/− mice develop spontaneous HCC. Moreover, low expression of HJV or hepcidin (HAMP) mRNAs predicts poor prognosis in HCC patients. We conclude that Hjv has a hepatoprotective function and its deficiency in mice promotes mitochondrial dysfunction and hepatocarcinogenesis.
Association Between the Onset of Physical Frailty and Executive Function in Community-Dwelling Elderly People
Authors: Toda Atsushi , Yano Jitsuro , Tanemura Jun 
Published: February 2022

Purpose:
Physical frailty may increase the risk of dementia, but it is not known exactly how cognition decreases. In this study, the features of recognition dysfunction in physical frailty were assessed.

Method:

The subjects were 46 elderly people aged 75 years or older (
M
age
= 83.2 ± 5.1 years) who visited community day care facilities between July 2018 and January 2020. The subjects were divided into a physical frailty group and a nonfrailty group, and physical performance and cognitive function were evaluated. Physical performance was measured by the Timed Up and Go (TUG) test, handgrip strength, lower leg circumference on both sides, and one-leg standing time. The Mini-Mental State Examination, Raven's Colored Progressive Matrices, and the Trail Making Test (TMT) were used to assess cognitive function.

Results:

The subjects were diagnosed based on the Cardiovascular Health Study criteria, in particular, Cardiovascular Health Study diagnostic items based on the Japanese version criteria. The physical frailty group included 10 subjects with an average age of 82.9 ± 4.0 years, and the nonfrailty group included 18 subjects with an average age of 83.4 ± 3.9 years. The physical frailty group showed significantly lower TUG and TMT compared with the nonfrailty group. There was also a significant correlation between TUG and Part B of the TMT in the physical frailty group (r = 0.735,
p
< .05).

Conclusions:
Executive function was lower in the physical frailty group, and the possibility of an effect on physical activity was suggested. Based on these results, evaluation of physical frailty can lead to more strategic prevention and treatment by combining physical performance evaluation with cognitive function tests including evaluation of executive function.
Privacy‐preserving blockchain‐based authentication and trust management in VANETs
Authors: Ahmed Waheeb , Di Wu , Mukathe Daniel 
Published: February 2022

AbstractVehicular Ad Hoc Networks (VANETs) are characterized by high mobility of nodes and volatility, which make privacy, trust management, and security challenging issues in VANETs' design. In such networks, data can be exposed to a variety of attacks, the most dangerous is false information dissemination, which threatens the safety and efficiency of transportation systems. False emergency messages can be injected by inside attackers to announce fake incidents such as traffic accidents, resulting in a false information attack. As the data in VANET is based on events, any trust mechanism must first identify the true events. To address these security challenges, a blockchain‐based authentication scheme and trust management model are proposed for VANETs. Using the authentication scheme, vehicles are enabled to send messages anonymously to the roadside units (RSUs) and the identity privacy of vehicles is protected. Besides, the proposed trust management model is designed to detect and deal with false information by evaluating the trustworthiness of vehicles and data. Using the trust model, when vehicles report an incident to the nearest RSU, the RSU is able to verify whether or not the incident took place. This mechanism ensures that RSUs send only verified event notifications. Finally, RSUs participate in updating the trust values of vehicles and store these values in the blockchain. The efficiency of the proposed authentication scheme is validated through analysis while the trust model is validated through simulations. The results obtained show that the proposed authentication scheme and the trust model provide better performance than other state‐of‐the‐art models where malicious vehicles can be identified efficiently and RSUs are enabled to broadcast only legitimate events.
New self-consistent wind parameters to fit optical spectra of O-type stars observed with the HERMES spectrograph
Authors: Gormaz-Matamala A. C. , Curé M. , Lobel A. , Panei J. A. , Cuadra J. , Araya I. , Arcos C. , Figueroa-Tapia F. 
Published: February 2022

Aims. We performed a spectral fitting for a set of O-type stars based on self-consistent wind solutions, which provide mass-loss rate and velocity profiles directly derived from the initial stellar parameters. The great advantage of this self-consistent spectral fitting is therefore the reduction of the number of free parameters to be tuned.
Methods. Self-consistent values for the line-force parameters (k, α, δ)sc and subsequently for the mass-loss rate, Msc, and terminal velocity, υ∞‚sc, are provided by the m-CAK prescription introduced in Paper I, which is updated in this work with improvements such as a temperature structure T(r) for the wind that are self-consistently evaluated from the line-acceleration. Synthetic spectra were calculated using the radiative transfer code FASTWIND, replacing the classical β-law for our new calculated velocity profiles v(r) and therefore making clumping the only free parameter for the stellar wind.
Results. We found that self-consistent m-CAK solutions provide values for theoretical mass-loss rates of the order of the most recent predictions of other studies. From here, we generate synthetic spectra with self-consistent hydrodynamics to fit and obtain a new set of stellar and wind parameters for our sample of O-type stars (HD 192639, 9 Sge, HD 57682, HD 218915, HD 195592, and HD 210809), whose spectra were taken with the high-resolution echelle spectrograph HERMES (R = 85 000). We find a satisfactory global fit for our observations, with a good accuracy for photospheric He I and He II lines and a quite acceptable fit for H lines. Although this self-consistent spectral analysis is currently constrained in the optical wavelength range alone, this is an important step towards the determination of stellar and wind parameters without using a β-law. Based on the variance of the line-force parameters, we establish that our method is valid for O-type stars with Teff ≥ 30 kK and log g ≥ 3.2. Given these results, we expect that the values introduced here are helpful for future studies of the stars constituting this sample, together with the prospect that the m-CAK self-consistent prescription may be extended to numerous studies of massive stars in the future.
The Influence Of Individual Stars On The long-Term Dynamics Of Comets C/2014 UN271 And C/2017 K2
Authors: Dybczyński Piotr A. , Królikowska Małgorzata 
Published: February 2022

Context. In June 2021, the discovery of an unusual comet C/2014 UN271 (Bernardinelli-Bernstein) was announced. Its cometary activity beyond the orbit of Uranus has also refreshed interest in similar objects, including C/2017 K2 (PANSTARRS). Another peculiarity of these objects is the long interval of positional data, taken at large heliocentric distances.
Aims. These two comets are suitable candidates for a detailed investigation of their long-term motion outside the planetary zone. Using the carefully selected orbital solutions, we aim to estimate the orbital parameters of their orbits at the previous perihelion passage. This might allow us to discriminate between dynamically old and new comets.
Methods. To follow the dynamical evolution of long-period comets far outside the planetary zone, it is necessary to take into account both the perturbation caused by the overall Galactic gravitational potential and the actions of individual stars appearing in the solar neighborhood. To this aim, we applied the recently published methods based on the ephemerides of stellar perturbers.
Results. For C/2014 UN271, we obtained a precise orbital solution that can be propagated into the past and the future. For C/2017 K2, we have to limit ourselves to studying the past motion because some signs of nongravitational effects can be found in recent positional observations. Therefore, we use a specially selected orbital solution suitable for past motion studies. Using these starting orbits, we propagated both comets to their previous perihelia. We also investigated the future motion of C/2014 UN271.
Conclusions. The orbital evolution of these two comets appears to be sensitive to perturbations from several stars that closely approach the Sun. To the detriment of our analysis, the errors on the 6D data for some of these stars are too large to obtain definitive results for the studied comets; nevertheless, we deduce that both comets were probably outside the planetary zone in the previous perihelion.