bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional regulators and alterations that drive melanoma initiation and progression
Authors: Gupta Romi , Janostiak Radoslav , Wajapeyee Narendra 
Published: October 2020

AbstractAlthough melanoma is the least frequent type of skin cancer, it accounts for the majority of skin cancer-related deaths. Large-scale sequencing efforts have led to the classification of melanoma into four major subtypes (i.e., BRAF-mutant, NRAS-mutant, NF1-deficient, and triple wild-type). These sequencing studies have also revealed that melanoma genomes are some of the most mutated genomes of all cancers and therefore have a high neoantigen load. These findings have resulted in the development and clinical use of targeted therapies against the oncogenic BRAF→MEK→ERK pathway and immune checkpoint inhibitors for the treatment of metastatic melanoma. Although some patients with metastatic melanoma benefit immensely from these transformative therapies, others either become resistant or do not respond at all. These clinical challenges have intensified the search for new drug targets and drugs that can benefit patients who are either intrinsically resistant or have acquired resistance to targeted therapies and immunotherapies. Numerous signaling pathways and oncogenic drivers can cause changes in mRNA transcription that in turn drive melanoma initiation and progression. Transcriptional regulation of mRNA expression is necessary to maintain cell identity and cellular plasticity via the regulation of transcription factor expression and function, promoter/enhancer activities, chromatin regulators, and three-dimensional genome organization. Transcriptional deregulation can arise due to genetic and/or non-genetic alterations in the genome. Specifically, these deregulated transcriptional programs can become liabilities for melanoma cells due to their acquired dependencies on these programs for survival, which can be harnessed to develop new therapies for melanoma. In this article, we present an overview of the mechanisms that result in the transcriptional deregulation of mRNA expression in melanoma cells and assess how these changes facilitate melanoma initiation and progression. We also describe how these deregulated transcriptional pathways represent new opportunities for the development of unconventional and potentially impactful treatments for metastatic melanoma.
Association of post-diagnostic use of cholera vaccine with survival outcome in breast cancer patients
Authors: Zheng Guoqiao , Sundquist Jan , Sundquist Kristina , Ji Jianguang 
Published: October 2020

Abstract
Background
Expensive cancer treatment calls for alternative ways such as drug repurposing to develop effective drugs. The aim of this study was to analyse the effect of post-diagnostic use of cholera vaccine on survival outcome in breast cancer patients.

Methods
Cancer diagnosis and cholera vaccination were obtained by linkage of several Swedish national registries. One vaccinated patient was matched with maximum two unvaccinated individuals based on demographic, clinical and socioeconomic factors. We performed proportional Cox regression model to analyse the differences in overall and disease-specific survivals between the matched patients.

Results
In total, 617 patients received cholera vaccine after breast cancer diagnosis. The median (interquartile range) time from diagnosis to vaccination was 30 (15–51) months and from vaccination to the end of follow-up it was 62 (47–85) months. Among them, 603 patients were matched with 1194 unvaccinated patients. Vaccinated patients showed favourable overall survival (hazard ratio (HR): 0.54, 95% confidence interval (CI): 0.37–0.79) and disease-specific survival (HR: 0.53, 95% CI: 0.33–0.84), compared to their unvaccinated counterpart. The results were still significant in multiple sensitivity analyses.

Conclusions
Post-diagnostic use of cholera vaccine is associated with a favourable survival rate in breast cancer patients; this provides evidence for repurposing it against breast cancer.
Small GTPase RAB6 deficiency promotes alveolar progenitor cell renewal and attenuates PM2.5-induced lung injury and fibrosis
Authors: Yang Lawei , Liu Gang , Li Xiaomin , Xia Zhengyuan , Wang Yahong , Lin Weihao , Zhang Wei , Zhang Wenjuan , Li Xuenong 
Published: October 2020

AbstractIdiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by chronic non-specific inflammation of the interstitial lung and extensive deposition of collagen fibers leading to destruction of lung function. Studies have demonstrated that exposure to fine particulate matter (PM2.5) increases the risk of IPF. In order to recover from PM2.5-induced lung injury, alveolar epithelial cells need to be repaired and regenerated to maintain lung function. Type 2 alveolar epithelial cells (AEC2) are stem cells in the adult lung that contribute to the lung repair process through complex signaling. Our previous studies demonstrated that RAB6, a RAS family member lowly expressed in lung cancer, inhibited lung cancer stem cell self-renewal, but it is unclear whether or not and how RAB6 may regulate AEC2 cell proliferation and self-renewal in PM2.5-induced pulmonary fibrosis. Here, we demonstrated that knockout of RAB6 inhibited pulmonary fibrosis, oxidative stress, and AEC2 cell death in PM2.5-injured mice. In addition, knockout of RAB6 decreased Dickkopf 1(DKK1) autocrine and activated proliferation, self-renewal, and wnt/β-catenin signaling of PM2.5-injured AEC2 cells. RAB6 overexpression increased DKK1 autocrine and inhibited proliferation, self-renewal and wnt/β-catenin signaling in AEC2 cells in vitro. Furthermore, DKK1 inhibitors promoted proliferation, self-renewal and wnt/β-catenin signaling of RAB6 overexpressing AEC2 cells, and attenuated PM2.5-induced pulmonary fibrosis in mice. These data establish RAB6 as a regulator of DKK1 autocrine and wnt/β-catenin signal that serves to regulate AEC2 cell proliferation and self-renewal, and suggest a mechanism that RAB6 disruption may promote AEC2 cell proliferation and self-renewal to enhance lung repair following PM2.5 injury.
Autophagy facilitates adaptation of budding yeast to respiratory growth by recycling serine for one-carbon metabolism
Authors: May Alexander I. , Prescott Mark , Ohsumi Yoshinori 
Published: October 2020

AbstractThe mechanism and function of autophagy as a highly-conserved bulk degradation pathway are well studied, but the physiological role of autophagy remains poorly understood. We show that autophagy is involved in the adaptation of Saccharomyces cerevisiae to respiratory growth through its recycling of serine. On respiratory media, growth onset, mitochondrial initiator tRNA modification and mitochondrial protein expression are delayed in autophagy defective cells, suggesting that mitochondrial one-carbon metabolism is perturbed in these cells. The supplementation of serine, which is a key one-carbon metabolite, is able to restore mitochondrial protein expression and alleviate delayed respiratory growth. These results indicate that autophagy-derived serine feeds into mitochondrial one-carbon metabolism, supporting the initiation of mitochondrial protein synthesis and allowing rapid adaptation to respiratory growth.
Putative biomarkers for early diagnosis and prognosis of congenital ocular toxoplasmosis
Authors: de Araújo Thádia Evelyn , dos Santos Luara Isabela , Gomes Angelica Oliveira , Carneiro Ana Carolina Aguiar Vasconcelos , Machado Anderson Silva , Coelho-dos-Reis Jordana Grazziela , Peruhype-Magalhães Vanessa , Béla Samantha Ribeiro , Andrade Gláucia Manzan Queiroz , Vasconcelos-Santos Daniel Vitor , Januário José Nélio , Teixeira-Carvalho Andréa , Vitor Ricardo Wagner Almeida , do Valle Antonelli Lis Ribeiro , Ferro Eloisa Amália Vieira , Martins-Filho Olindo Assis ,   the UFMG Congenital Toxoplasmosis Brazilian Group UFMG-CTBG, beside the authors, Azevedo Danuza O. Machado , Carellos Ericka V. Machado , Resende Luciana Macedo , Romanelli Roberta M. Castro 
Published: October 2020

AbstractIn the present study we have evaluated the performance of several immunological biomarkers for early diagnosis and prognosis of congenital toxoplasmosis. Our results showed that ex vivo serum levels of CXCL9, and the frequencies of circulating CD4+CD25+T-cells andT. gondii-specific IFN-γ+CD4+T-cells measured 30–45 days after birth presented high accuracy to distinguishT. gondii-infected infants from healthy age-matched controls (Global Accuracy/AUC = 0.9; 0.9 and 0.8, respectively). Of note was the enhanced performance (Accuracy = 96%) achieved by using a combined stepwise analysis of CD4+CD25+T-cells and CXCL9. In addition, high global accuracy (AUC = 0.9) with elevated sensitivity (Se = 98%) was also reached by using the total frequency of in vitro IFN-γ-producingT. gondii-specific T-cells (∑ IFN-γ+CD4+& CD8+) as a biomarker of congenital toxoplasmosis. Furthermore, the analysis of in vitroT. gondii-specific IL5+CD4+T-cells and IFN-γ+NK-cells displayed a high accuracy for early prognosis of ocular lesion in infant with congenital toxoplasmosis (Global Accuracy/AUC = 0.8 and 0.9, respectively). Together, these findings support the relevance of employing the elements of the cell-mediated immune response as biomarkers with potential to endorse early diagnosis and prognosis of congenital ocular toxoplasmosis to contribute for a precise clinical management and effective therapeutic intervention.
Acute cardiovascular health effects in a panel study of personal exposure to traffic-related air pollutants and noise in Toronto, Canada
Authors: Biel Rita , Danieli Coraline , Shekarrizfard Maryam , Minet Laura , Abrahamowicz Michal , Baumgartner Jill , Liu Rick , Hatzopoulou Marianne , Weichenthal Scott 
Published: October 2020

AbstractUrban populations are often simultaneously exposed to air pollution and environmental noise, which are independently associated with cardiovascular disease. Few studies have examined acute physiologic responses to both air and noise pollution using personal exposure measures. We conducted a repeated measures panel study of air pollution and noise in 46 non-smoking adults in Toronto, Canada. Data were analyzed using linear mixed-effects models and weighted cumulative exposure modeling of recent exposure. We examined acute changes in cardiovascular health effects of personal (ultrafine particles, black carbon) and regional (PM2.5, NO2, O3, Ox) measurements of air pollution and the role of personal noise exposure as a confounder of these associations. We observed adverse changes in subclinical cardiovascular outcomes in response to both air pollution and noise, including changes in endothelial function and heart rate variability (HRV). Our findings show that personal noise exposures can confound associations for air pollutants, particularly with HRV, and that impacts of air pollution and noise on HRV occur soon after exposure. Thus, both noise and air pollution have a measurable impact on cardiovascular physiology. Noise should be considered alongside air pollution in future studies to elucidate the combined impacts of these exposures in urban environments.
Iodine staining as a useful probe for distinguishing insulin amyloid polymorphs
Authors: Hiramatsu Takato , Yamamoto Naoki , Ha Seongmin , Masuda Yuki , Yasuda Mitsuru , Ishigaki Mika , Yuzu Keisuke , Ozaki Yukihiro , Chatani Eri 
Published: October 2020

AbstractIt is recently suggested that amyloid polymorphism, i.e., structural diversity of amyloid fibrils, has a deep relationship with pathology. However, its prompt recognition is almost halted due to insufficiency of analytical methods for detecting polymorphism of amyloid fibrils sensitively and quickly. Here, we propose that iodine staining, a historically known reaction that was firstly found by Virchow, can be used as a method for distinguishing amyloid polymorphs. When insulin fibrils were prepared and iodine-stained, they exhibited different colors depending on polymorphs. Each of the colors was inherited to daughter fibrils by seeding reactions. The colors were fundamentally represented as a sum of three absorption bands in visible region between 400 and 750 nm, and the bands showed different titration curves against iodine, suggesting that there are three specific iodine binding sites. The analysis of resonance Raman spectra and polarization microscope suggested that several polyiodide ions composed of I3− and/or I5− were formed on the grooves or the edges of β-sheets. It was concluded that the polyiodide species and conformations formed are sensitive to surface structure of amyloid fibrils, and the resultant differences in color will be useful for detecting polymorphism in a wide range of diagnostic samples.
Prediction of particles deposition in a dilute quasi-steady gravity current by Lagrangian markers: effect of shear-induced lift force
Authors: Koohandaz Ali , Khavasi Ehsan , Eyvazian Arameh , Yousefi Hamid 
Published: October 2020

AbstractA gravity current in a channel at the presence of a triangular obstacle was investigated using LES simulation and the Eulerian approach. The Saffman–Mei equation was also applied to examine the effect of shear-induced lift force on particle deposition. To this end, particles were considered as Lagrangian markers and injected into gravity current. It is important to keep in mind that the interaction between the gravity current and particles was treated as a one-way coupling. The results show that shear-induced lift force prevents particles to deposit at the entrance of channel, where the velocity gradient is high. Furthermore, a reduction in the rate of sediment deposition can be seen again in the vicinity of obstacle due to high velocity gradient. The important result is that the shear-induced lift force has an important role in the cases with considerable velocity gradient in quasi-steady flows and this force can affect the pattern of sedimentation over time. Q criterion is utilized to depict the vortical structures of flow. Vortical structures with larger diameter, that indicate stronger vortexes, has been seen in various sections of channel, especially in the region near the obstacle due to the presence of obstacle.
Predictive value of suvmax changes between two sequential post-therapeutic FDG-pet in head and neck squamous cell carcinomas
Authors: Stadler Thomas M. , Hüllner Martin W. , Broglie Martina A. , Morand Grégoire B. 
Published: October 2020

Abstract18-flurodesoxyglucose position emission tomography (FDG-PET) with computed tomography (CT) or magnetic resonance imaging (MRI) is a broadly accepted tool for pretherapeutic staging and post-therapeutic assessment of response. The prognostic value of sequential post-therapeutic FDG-PETs and the impact of change in metabolic activity has been scarcely reported so far. We hypothesized that an increase in metabolic activity (as measured by maximum standardized uptake value, SUVmax) would be predictive for recurrence. We retrospectively assessed all oral, oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma patients treated at the Department of Otorhinolaryngology—Head and Neck Surgery, University Hospital Zurich between April 1st, 2010 and September 30th, 2018 (N = 337). After a negative post-treatment FDG-PET at 3 months, we measured the SUVmax of the local tumor area and the regional lymph nodes on follow-up FDG-PET at 9 months. We then correlated SUVmax difference between 9 and 3 months with tumor recurrence using Kaplan Meier analysis. During follow-up, 68 patients (20.2%) had local recurrence and 53 had regional recurrence (15.7%) at a median time of 9.0 (IQR 4.25–14) and 7.0 (IQR 5.25–23) months, respectively. An increase in local and/or regional SUVmax from the 3 months to the 9 months post-therapeutic FDG-PET resulted in a poorer recurrence-free survival (Log rank, P = 0.001, for both). An increase in local SUVmax between 3 and 9 months was associated with a hazard ratio of 4.17 for recurrence (95%CI 1.89–9.2, P = 0.0003). In conclusion, an increase in metabolic activity/SUVmax between two post-therapeutic FDG-PETs requires a histological examination as it is associated with tumor recurrence.
Electrochemical growth and characterisation of ZnO nanostructures for dye‐sensitised solar cells
Authors: Dubey R.S. , Saravanan S. 
Published: October 2020

This Letter presents the electrodeposition of zinc oxide (ZnO) nanostructures by varying the negative potential and investigation of structural, optical, and morphological characteristics. UV–vis spectroscopy investigation showed the redshift of the absorption peak with the increased negative potential. Using Tauc relation, the optical bandgap values estimated to be 3.09, 2.97, 2.93, 2.91, 2.90, and 2.84 eV corresponding to the samples prepared at potential −0.5, −0.7, −0.9, −1.1, −1.3 and −1.5 V. Fluorescence spectra exhibited the UV emission band at wavelength 392 nm along with a peak at 650 nm corresponds to the second‐order nature of ZnO. Fourier‐transform infrared spectroscopy analysis confirmed the various vibration modes at 403, 493, and 702 cm−1 originated by the ZnO nanostructures. X‐ray diffraction pattern revealed the hexagonal wurtzite phase of ZnO. Scanning electron microscopy investigation evidenced the distinct morphology of ZnO with the increased negative potential; however, the dense and perpendicularly oriented ZnO nanorods are prepared at highest negative potential as compared to rice grain‐like ZnO structure prepared at least negative potential. Furthermore, the prepared nanostructures are used as dye‐sensitised solar cells (DSSCs) photoanodes, while the DSSC‐Z6 showed the increased cell efficiency up to 1.2%, due to the aligned growth of the ZnO nanorods.
Analyzing the propagation of EUV waves and their connection with type II radio bursts by combining numerical simulations and multi-instrument observations
Authors: Koukras A. , Marqué C. , Downs C. , Dolla L. 
Published: October 2020

Context. EUV (EIT) waves are wavelike disturbances of enhanced extreme ultraviolet (EUV) emission that propagate away from an eruptive active region across the solar disk. Recent years have seen much debate over their nature, with three main interpretations: the fast-mode magneto-hydrodynamic (MHD) wave, the apparent wave (reconfiguration of the magnetic field), and the hybrid wave (combination of the previous two).
Aims. By studying the kinematics of EUV waves and their connection with type II radio bursts, we aim to examine the capability of the fast-mode interpretation to explain the observations, and to constrain the source locations of the type II radio burst emission.
Methods. We propagate a fast-mode MHD wave numerically using a ray-tracing method and the WKB (Wentzel-Kramers-Brillouin) approximation. The wave is propagated in a static corona output by a global 3D MHD Coronal Model, which provides density, temperature, and Alfvén speed in the undisturbed coronal medium (before the eruption). We then compare the propagation of the computed wave front with the observed wave in EUV images (PROBA2/SWAP, SDO/AIA). Lastly, we use the frequency drift of the type II radio bursts to track the propagating shock wave, compare it with the simulated wave front at the same instant, and identify the wave vectors that best match the plasma density deduced from the radio emission. We apply this methodology for two EUV waves observed during SOL2017-04-03T14:20:00 and SOL2017-09-12T07:25:00.
Results. The simulated wave front displays a good qualitative match with the observations for both events. Type II radio burst emission sources are tracked on the wave front all along its propagation. The wave vectors at the ray-path points that are characterized as sources of the type II radio burst emission are quasi-perpendicular to the magnetic field.
Conclusions. We show that a simple ray-tracing model of the EUV wave is able to reproduce the observations and to provide insight into the physics of such waves. We provide supporting evidence that they are likely fast-mode MHD waves. We also narrow down the source region of the radio burst emission and show that different parts of the wave front are responsible for the type II radio burst emission at different times of the eruptive event.
A data-driven approach to constraining the atmospheric temperature structure of the ultra-hot Jupiter KELT-9b
Authors: Fossati L. , Shulyak D. , Sreejith A. G. , Koskinen T. , Young M. E. , Cubillos P. E. , Lara L. M. , France K. , Rengel M. , Cauley P. W. , Turner J. D. , Wyttenbach A. , Yan F. 
Published: October 2020

Context. Observationally constraining the atmospheric temperature-pressure (TP) profile of exoplanets is an important step forward for improving planetary atmosphere models, thus further enabling one to place the detection of spectral features and the measurement of atomic and molecular abundances through transmission and emission spectroscopy on solid ground.
Aims. The aim is to constrain the TP profile of the ultra-hot Jupiter KELT-9b by fitting synthetic spectra to the observed Hα and Hβ lines and identify why self-consistent planetary TP models are unable to fit the observations.
Methods. We constructed 126 one-dimensional TP profiles varying the lower and upper atmospheric temperatures, as well as the location and gradient of the temperature rise. For each TP profile, we computed the transmission spectra of the Hα and Hβ lines employing the Cloudy radiative transfer code, which self-consistently accounts for non-local thermodynamic equilibrium (NLTE) effects.
Results. The TP profiles, leading to best fit the observations, are characterised by an upper atmospheric temperature of 10 000–11 000 K and by an inverted temperature profile at pressures higher than 10−4 bar. We find that the assumption of local thermodynamic equilibrium (LTE) leads one to overestimate the level population of excited hydrogen by several orders of magnitude and hence to significantly overestimate the strength of the Balmer lines. The chemical composition of the best fitting models indicate that the high upper atmospheric temperature is most likely driven by metal photoionisation and that FeII and FeIII have comparable abundances at pressures lower than 10−6 bar, possibly making the latter detectable.
Conclusions. Modelling the atmospheres of ultra-hot Jupiters requires one to account for metal photoionisation. The high atmospheric mass-loss rate (>1011 g s−1), caused by the high temperature, may have consequences on the planetary atmospheric evolution. Other ultra-hot Jupiters orbiting early-type stars may be characterised by similarly high upper atmospheric temperatures and hence high mass-loss rates. This may have consequences on the basic properties of the observed planets orbiting hot stars.
Influence de la mécanique des fluides sur la formation des métastases
Authors: Follain Gautier , Gensbittel Valentin , Mary Benjamin , Lefebvre Olivier , Harlepp Sébastien , Hyenne Vincent , Goetz Jacky G. 
Published: October 2020

La suite d’évènements menant à l’apparition de métastases est appelée « cascade métastatique ». L’étude récente de la composante biomécanique de cette cascade a révélé le rôle central des liquides biologiques dans la dissémination métastatique. Tout en participant au transport des cellules tumorales circulantes et des facteurs qu’elles sécrètent, ces liquides circulants influencent cette cascade par les forces mécaniques qu’ils génèrent. Les propriétés hémodynamiques et les contraintes topologiques de l’architecture vasculaire contrôlent la formation de niches métastatiques et le potentiel métastatique des cellules tumorales.