bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual Inhibition of MEK and AXL Targets Tumor Cell Heterogeneity and Prevents Resistant Outgrowth Mediated by the Epithelial-to-Mesenchymal Transition in NSCLC
Authors: Konen Jessica M. , Rodriguez B. Leticia , Padhye Aparna , Ochieng Joshua K. , Gibson Laura , Diao Lixia , Fowlkes Natalie W. , Fradette Jared J. , Peng David H. , Cardnell Robert J. , Kovacs Jeffrey J. , Wang Jing , Byers Lauren A. , Gibbons Don L. 
Published: January 2021

Abstract

The epithelial-to-mesenchymal transition (EMT) is a dynamic epigenetic reprogramming event that occurs in a subset of tumor cells and is an initiating step toward invasion and distant metastasis. The process is reversible and gives plasticity to cancer cells to survive under variable conditions, with the acquisition of cancer stem cell–like characteristics and features such as drug resistance. Therefore, understanding survival dependencies of cells along the phenotypic spectrum of EMT will provide better strategies to target the spatial and temporal heterogeneity of tumors and prevent their ability to bypass single-inhibitor treatment strategies. To address this, we integrated the data from a selective drug screen in epithelial and mesenchymal KRAS/p53 (KP)-mutant lung tumor cells with separate datasets including reverse-phase protein array and an in vivo shRNA dropout screen. These orthogonal approaches identified AXL and MEK as potential mesenchymal and epithelial cell survival dependencies, respectively. To capture the dynamicity of EMT, incorporation of a dual fluorescence EMT sensor system into murine KP lung cancer models enabled real-time analysis of the epigenetic state of tumor cells and assessment of the efficacy of single agent or combination treatment with AXL and MEK inhibitors. Both two- and three-dimensional culture systems and in vivo models revealed that this combination treatment strategy of MEK plus AXL inhibition synergistically killed lung cancer cells by specifically targeting each phenotypic subpopulation. In conclusion, these results indicate that cotargeting the specific vulnerabilities of EMT subpopulations can prevent EMT-mediated drug resistance, effectively controlling tumor cell growth and metastasis.

Significance:
This study shows that a novel combination of MEK and AXL inhibitors effectively bypasses EMT-mediated drug resistance in KRAS/p53-mutant non–small cell lung cancer by targeting EMT subpopulations, thereby preventing tumor cell survival.
Small States in the UN Security Council: Austria’s Quest to Maintain Status
Authors: Thorhallsson Baldur , Eggertsdóttir Anna Margrét 
Published: January 2021

Summary
This article offers a case study on why small states seek membership on the UN Security Council (UNSC). It examines the intension of a small state, Austria, to seek membership on the Council for the 2009-2010 term, the campaign strategy and the domestic debate on the candidacy. The analysis indicates that Austria’s former status as an empire and successful transformation in the post-war period influenced its candidacy and campaign strategy. Also, Austria’s ideational commitment to the UN cause was the foundation for its successful UNSC campaign. Austria’s small size was not a hindrance in its campaign: on the contrary, as a small state Austria gained prestige for its competence and contributions to the UN. A UNSC seat for Austria was not a question of a small state seeking status; rather, it was a quest for remaining relevant and maintaining status in a changing world system.
Three Short Essays on Demodocus’s Song of Ares and Aphrodite (Odyssey 8.266–369)
Authors: Edmunds Lowell 
Published: January 2021

Abstract
First essay: Does an audience, ancient or modern, find Demodocus’s second song humorous? This much-discussed question can be replaced with another. What is the humor that the internal Olympian audience finds? Hephaestus averts potential derision of himself and turns laughter against Ares and Aphrodite, with Poseidon’s help ultimately winning the day.
Second essay: Demodocus’s song is not his, i.e., the poet’s, invention but a re-told story recognized by his audience as such.
Third essay: I analyze the particular form of the condition in Hermes’s reply to Apollo and offer two comparanda in Greek literature.
Metaphor in the Speech of Achilles (Iliad 9.308–429)
Authors: Zanker Andreas T. 
Published: January 2021

Abstract
This article offers an analysis of the conceptual metaphors lodged within a continuous block of Homeric text, Achilles’s famous speech in Iliad 9. It argues for the productivity of applying Conceptual Metaphor Theory (CMT) to Homer, while also contributing to the debate concerning the diachronic roots of modern conventional metaphors. Topics considered include (1) Achilles’s extension, confirmation, and modification of the metaphors used elsewhere in the epics, (2) the different layers of metaphorical usage found in Homer, and (3) the hero’s questioning of one prevalent Homeric metaphor in his rejection of Agamemnon’s gifts as a motivation to fight.
Water-Jet Cavitation Shock Bulging as Novel Microforming Technique
Authors: Li Fuzhu , Fan Haiyang , Guo Yuqin , Chen Zhipeng , Wang Xu , Li Ruitao , Liu Hong , Wang Yun 
Published: January 2021

AbstractWith the continuous expansion of the application range of microelectromechanical systems, microdevice forming technology has achieved remarkable results. However, it is challenging to develop new microforming processes that are low cost, environmentally friendly, and highly flexible; the high-energy shock wave in a cavitation bubble’s collapse process is used as the loading force. Herein, a new process for the microbulging of the water-jet cavitation is proposed. A series of experiments involving the water-jet cavitation shock microbulging process for TA2 titanium foil is performed on an experimental system. The microforming feasibility of the water-jet cavitation is investigated by characterizing the shape of the formed part. Subsequently, the effects of the main parameters of the water-jet cavitation on the bulging profile, forming depth, surface roughness, and bulging thickness distribution of TA2 titanium foil are revealed. The results show that the plastic deformation increases nonlinearly with the incident pressure. When the incident pressure is 20 MPa, the maximum deformation exceeds 240 μm, and the thickness thinning ratio changes within 10%. The microbulging feasibility of water-jet cavitation is verified by this phenomenon.
The potential of high-speed rail freight in Europe: how is a modal shift from road to rail possible for low-density high value cargo?
Authors: Boehm Mathias , Arnz Marlin , Winter Joachim 
Published: January 2021

Abstract
Purpose
A fully electrified transport chain offers considerable potential for CO2 savings. In this paper, we examine the conditions necessary to introduce a fully electrified, large-scale, high-speed rail freight transport system in Europe in addition to high-speed passenger trains, aiming to shift goods transport from road to rail. We compare a novel high-speed rail freight concept with road-based lorry transport for low-density high value goods to estimate the potential for a modal shift from road to rail in 2030.

Methods
To characterize the impacts of different framework conditions, a simulation tool was designed as a discrete choice model, based on random utility theory, with integrated performance calculation assessing the full multimodal transport chain regarding costs, emissions and time. It was applied to a European reference scenario based on forecast data for freight traffic in 2030.

Results
We show that high-speed rail freight is about 70% more expensive than the conventional lorry but emits 80% less CO2 emissions for the baseline parameter setting. The expected mode share largely depends on the cargo’s value of time, while the implementation of a CO2-tax of 100 EUR/tCO2eq has an insignificant impact. The costs of handling goods and the infrastructure charges are highly influential variables.

Conclusion
High-speed rail track access charges are a suitable political instrument to create a level playing field between the transport modes and internalize external costs of freight transport. With the given access charge structure, a reduction of the maximum operating speed to 160 km/h has a positive impact on the expected mode share of rail transport while it still reacts positively to a wide range of the cargo’s time sensitivity (compared to a maximum operating speed of 350 km/h). The flexibility of rail freight’s operating speed is important for an effective implementation. Further research should concentrate on time- and cost-efficient transhipment terminals as they have a significant impact on transport performance.
Diagnostic yield and appropriate indication of upper endoscopy in Jordanian children
Authors: Altamimi Eyad , Odeh Yousef , Al-quraan Tuka , Mohamed Elmi , Rawabdeh Naif 
Published: January 2021

Abstract
Background
Upper endoscopy is an essential tool for diagnosing pediatric gastrointestinal issues. This study aimed to assess the indications, diagnostic yields, concordance between histopathological and endoscopic findings and suitability of upper endoscopies performed at a tertiary university hospital in Jordan.

Methods
Hospital records of children who underwent upper endoscopy were retrospectively reviewed. Demographics, endoscopic details (e.g., indications, findings and any complications), and histopathological findings were collected. The relationship between endoscopic findings and histopathological abnormalities was reported.

Results
The study included 778 patients (age, 92.5 ± 54.5 months; 380 girls, 48.8%). The most common age group was children younger than 60 months (273 patients, 34.3%). The most common indication for endoscopy was abdominal pain, followed by vomiting and failure to thrive or weight loss. Normal upper endoscopy was reported in 411 patients (52.8%). Age below 60 months, abdominal pain, dysphagia/odynophagia, and heartburn were predictive of abnormal endoscopy in multivariate analysis with p-value 0.000, 0.048, 0.001 and 0.01 respectively. Abnormal endoscopy showed 67.3% sensitivity and 69.9% specificity to predict histopathological abnormalities. Of those performed, 13.6% endoscopies were described as inappropriate indication. The suitability of the procedure was a sensitive predictor for abnormal endoscopic and histopathological findings.

Conclusions
Abdominal pain is the most common indication for upper endoscopy in our population. It is associated with a higher chance of abnormal endoscopy. Concordance between endoscopic and histopathological findings is not high. Normal endoscopic findings shouldn`t discourage the endoscopist from obtaining tissue biopsies. Considering more biopsies may improve pathological detection rates. Compliance with established endoscopy guidelines may reduce unnecessary procedures.
Risk factors for osteoradionecrosis of the jaw in patients with head and neck squamous cell carcinoma
Authors: Kubota Hikaru , Miyawaki Daisuke , Mukumoto Naritoshi , Ishihara Takeaki , Matsumura Megumi , Hasegawa Takumi , Akashi Masaya , Kiyota Naomi , Shinomiya Hirotaka , Teshima Masanori , Nibu Ken-ichi , Sasaki Ryohei 
Published: January 2021

Abstract
Background
To evaluate factors associated with osteoradionecrosis of the jaw (ORNJ) in patients with head and neck squamous cell carcinoma (HNSCC), focusing on jaw-related dose–volume histogram (DVH) parameters.

Methods
We retrospectively reviewed the medical records of 616 patients with HNSCC treated with curative-intent or postoperative radiation therapy (RT) during 2008–2018. Patient-related (age, sex, history of smoking or alcohol use, diabetes mellitus, performance status, pre-RT dental evaluation, pre- or post-RT tooth extraction), tumor-related (primary tumor site, T-stage, nodal status), and treatment-related (pre-RT surgery, pre-RT mandible surgery, induction or concurrent chemotherapy, RT technique) variables and DVH parameters (relative volumes of the jaw exposed to doses of 10 Gy–70 Gy [V10–70]) were investigated and compared between patients with and without ORNJ. The Mann–Whitney U test was used to compare RT dose parameters. Univariate and multivariate Cox regression analyses were used to assess factors associated with ORNJ development. Kaplan–Meier analyses were performed for cumulative ORNJ incidence estimation.

Results
Forty-six patients (7.5%) developed ORNJ. The median follow-up duration was 40 (range 3–145) months. The median time to ORNJ development was 27 (range 2–127) months. DVH analysis revealed that V30–V70 values were significantly higher in patients with than in those without ORNJ. In univariate analyses, primary tumor site, pre-RT mandible surgery, post-RT tooth extraction, and V60 > 14% were identified as important factors. In multivariate analyses, V60 > 14% (p = 0.0065) and primary tumor site (p = 0.0059) remained significant. The 3-year cumulative ORNJ incidence rates were 2.5% and 8.6% in patients with V60 ≤ 14% and > 14%, respectively (p < 0.0001), and 9.3% and 1.4% in patients with oropharyngeal or oral cancer and other cancers, respectively (p < 0.0001).

Conclusions
V60 > 14% and oropharyngeal or oral cancer were found to be independent risk factors for ORNJ. These findings might be useful to minimize ORNJ incidence in HNSCC treated with curative RT.
Conditional genetic deletion of CSF1 receptor in microglia ameliorates the physiopathology of Alzheimer’s disease
Authors: Pons Vincent , Lévesque Pascal , Plante Marie-Michèle , Rivest Serge 
Published: January 2021

Abstract
Background
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia in the world. Microglia are the innate immune cells of CNS; their proliferation, activation, and survival in pathologic and healthy brain have previously been shown to be highly dependent on CSF1R.

Methods
Here, we investigate the impact of such receptor on AD etiology and microglia. We deleted CSF1R using Cre/Lox system; the knockout (KO) is restricted to microglia in the APP/PS1 mouse model. We induced the knockout at 3 months old, before plaque formation, and evaluated both 6- and 8-month-old groups of mice.

Results
Our findings demonstrated that CSF1R KO did not impair microglial survival and proliferation at 6 and 8 months of age in APP cKO compared to their littermate-control groups APPSwe/PS1. We have also shown that cognitive decline is delayed in CSF1R-deleted mice. Ameliorations of AD etiology are associated with a decrease in plaque volume in the cortex and hippocampus area. A compensating system seems to take place following the knockout, since TREM2/β-Catenin and IL-34 expression are significantly increased. Such a compensatory mechanism may promote microglial survival and phagocytosis of Aβ in the brain.

Conclusions
Our results provide new insights on the role of CSF1R in microglia and how it interacts with the TREM2/β-Catenin and IL-34 system to clear Aβ and ameliorates the physiopathology of AD.
Accelerometry to study fine-scale activity of invasive Burmese pythons (Python bivittatus) in the wild
Authors: Whitney Nicholas M. , White Connor F. , Smith Brian J. , Cherkiss Michael S. , Mazzotti Frank J. , Hart Kristen M. 
Published: January 2021

AbstractBackgroundThe establishment of Burmese pythons (Python bivittatus)in Everglades National Park, Florida, USA, has been connected to a > 90% decline in the mesomammal population in the park and is a major threat to native reptile and bird populations. Efforts to control this population are underway, but are hampered by a lack of information about fine-scale activity cycles and ecology of these cryptic animals in the wild. We aimed to establish a technique for monitoring the activity of Burmese pythons in the wild using acceleration data loggers (ADLs), while attempting to identify any behavioral patterns that could be used to help manage this invasive species in the Greater Everglades and South Florida.ResultsWe obtained continuous acceleration and temperature data from four wild snakes over periods of 19 to 95 days (mean 54 ± 33 days). Snakes spent 86% of their time at rest and 14% of their time active, including transiting between locations. All snakes showed at least one period of continuous transiting lasting 10 h or more, with one animal transiting continuously for a period of 58.5 h. Acceleration data logger-derived transiting bout duration was significantly correlated with the distance snakes traveled per hour for two snakes that also carried GPS loggers. Snakes were most active in midday or early-night depending on individual and time of year, but all snakes were least likely to be active in the early mornings (0400–0700 h local time). Very little movement took place at temperatures below 14 °C or above 24 °C, with most movement taking place between 15° and 20 °C. One animal showed a highly unusual rolling event that may be indicative of a predation attempt, but this could not be confirmed.ConclusionsFine-scale activity and some behaviors were apparent from ADL data, making ADLs a potentially valuable, unbiased tool for monitoring large-bodied snakes in the wild. Snakes spent the majority of their time resting, but also moved continuously for several hours at a time during bouts of transiting. Results suggest that individuals may shift their diel activity pattern based on season. Understanding seasonal differences in activity levels can improve the accuracy of population estimates, help detect range expansion, and improve managers’ ability to find and capture individuals.
The funhouse mirror: the I in personalised healthcare
Authors: Vegter Mira W. , Zwart Hub A. E. , van Gool Alain J. 
Published: January 2021

AbstractPrecision Medicine is driven by the idea that the rapidly increasing range of relatively cheap and efficient self-tracking devices make it feasible to collect multiple kinds of phenotypic data. Advocates ofN = 1 research emphasize the countless opportunities personal data provide for optimizing individual health. At the same time, using biomarker data for lifestyle interventions has shown to entail complex challenges. In this paper, we argue that researchers in the field of precision medicine need to address the performative dimension of collecting data. We propose the fun-house mirror as a metaphor for the use of personal health data; each health data source yields a particular type of image that can be regarded as a ‘data mirror’ that is by definition specific and skewed. This requires competence on the part of individuals to adequately interpret the images thus provided.
Hypoglycemic episodes in hospitalized people with diabetes in Portugal: the HIPOS-WARD study
Authors: Alão Sílvia , Conceição João , Dores Jorge , Santos Lèlita , Araújo Francisco , Pape Estevão , Reis Mónica , Chipepo Árcia , Nascimento Edite , Baptista Ana , Pires Vanessa , Marques Carlos , Lages Adriana De Sousa , Pelicano-Romano João , de Jesus Paula M. 
Published: January 2021

Abstract
Background
We intended to estimate the proportion hypoglycemic/hyperglycemic emergency episodes in treated diabetes mellitus (DM) patients admitted to a hospital ward, and calculate the prevalence of risk factors for hypoglycemia and diabetic complications.

Methods
In this cross-sectional, multicentered study, the observational data was collected by physicians from patient’s hospitalization to discharge/death. Statistical tests were 2-tailed considering 5% significance level.

Results
There were 646 ward admissions due to hyperglycemic emergencies and 176 hypoglycemic episodes with a ratio hypoglycemia/hyperglycemia 0.27 for all DM patients. In T2DM patients the ratio was 0.38. These were mainly female (55.1%), functionally dependent (61.4%) and retired/disabled (73.1%). Median age was 75 years and median duration of disease 11 years. Half the patients were on insulin-based therapy and 30.1% on secretagogue-based therapy. Approximately 57% of patients needed occasional/full assistance to manage the disease. The most frequent risk factor for hypoglycemia was polypharmacy (85.0%). Hypoglycemia in the 12 months before admission was higher in insulin-based therapy patients (66.1%; p = 0.001).

Conclusions
Hyperglycemic emergencies are the most frequent cause of hospitalization in Portugal, although severe hypoglycemic events represent a health and social problem in elderly/frail patients. There is still the need to optimize therapy in terms of the potential for hypoglycemia in this patient group and a review of anti-hyperglycemic agents to add on to insulin.
The role of serotonin and diet in the prevalence of irritable bowel syndrome: a systematic review
Authors: Bruta Khushi , Vanshika  , Bhasin Kishnoor , Bhawana  
Published: January 2021

AbstractSerotonin or 5-hydroxytryptamine (5-HT)- a neurotransmitter of both the Enteric Nervous System and the Central Nervous System is synthesized by the hydroxylation of L- tryptophan to 5-hydroxytryptophan.Serotonin has been associated with gut functions like assimilation and absorption, alongside the regulation of particle transport and fluid discharge in the gastrointestinal tract and its deficiency is found to be a prominent factor in the prevalence of gut disorders like Irritable Bowel Syndrome.For this review, we assessed the conventional treatment methods of common drugs, with the recently accredited treatment options like dietary regulation, exercise, meditation, and acupuncture. Having found that the most commonly used drugs exhibited various side effects like nausea, fatigue, rash, and dizziness, an in-depth evaluation of different Indian dietary patterns and their respective effects on tryptophan levels has been highlighted to formulate an ideal diet for patients with Irritable Bowel Syndrome (IBS). This review seeks to explore the numerous studies conducted to link IBS with the lack of serotonin production in the body, alongside exploring the evidence associating certain foods with raised tryptophan levels to hypothesize a suitable Indian diet.This review, in its essence, stresses the crucial need for further research on the dietary implications of common Indian foods and their FODMAP (Fermented Oligosaccharides, Disaccharides, Monosaccharides, And Polyols) contents, while underscoring the benefits of using unconventional and natural methods for the treatment of tryptophan-related gut disorders.