bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Horizontal Mixing-Length Formulation for Numerical Simulations of Tropical Cyclones
Authors: Wang Weiguo , Liu Bin , Zhu Lin , Zhang Zhan , Mehra Avichal , Tallapragada Vijay 
Published: February 2021

AbstractA new physically based horizontal mixing-length formulation is introduced and evaluated in the Hurricane Weather and Research Forecasting (HWRF) Model. Recent studies have shown that the structure and intensity of tropical cyclones (TCs) simulated by numerical models are sensitive to horizontal mixing length in the parameterization of horizontal diffusion. Currently, many numerical models including the operational HWRF Model formulate the horizontal mixing length as a fixed fraction of grid spacing or a constant value, which is not realistic. To improve the representation of the horizontal diffusion process, the new formulation relates the horizontal mixing length to local wind and its horizontal gradients. The resulting horizontal mixing length and diffusivity are much closer to those derived from field measurements. To understand the impact of different mixing-length formulations, we analyze the evolutions of an idealized TC simulated by the HWRF Model with the new formulation and with the current formulation (i.e., constant values) of horizontal mixing length. In two real-case tests, the HWRF Model with the new formulation produces the intensity and track forecasts of Hurricanes Harvey (2017) and Lane (2018) that are much closer to observations. Retrospective runs of hundreds of forecast cycles of multiple hurricanes show that the mean errors in intensity and track simulated by HWRF with the new formulation can be reduced approximately by 10%.
GEOLIFE – Geomaterials for the environment, technology and human activities. Preface to the October 2014 special set of papers arising from presentations at the Goldschmidt 2013 conference
Authors: Giere R. , Oberti R. , Quartieri S. , Wogelius R. 
Published: February 2021

This special issue of the Mineralogical Magazine springs from the session we organized as part of the Goldschmidt 2013 conference in Florence. The title we proposed “GEOLIFE – Geomaterials for environment, technology and human activities” reflects our feeling that a wise use of the expertise gained by mineralogists while studying the crystal chemistry, as well as the chemical and physical properties of minerals in rocks and soils, still plays an important role in what is called “The cutting edge in Mineralogy and Mineral Physics”.Indeed, the current expertise in the physical, chemical and structural characterization of geomaterials, i.e. minerals, rocks and their synthetic analogues, now allows us to design innovative applications both for technological and environmental purposes. During the meeting we discussed some frontier work on phases produced naturally by the Earth ‘laboratory’ or fabricated within academic laboratories, which have the potential to improve the quality of life for current and future generations.
CHEK1 and circCHEK1_246aa Promote Multiple Myeloma Malignancy By Evoking Chromosomal Instability and Bone Lesion
Authors: Yang Ye , Gu Chunyan , Wang Wang , Tang Xiaozhu 
Published: February 2021

Key findings
CHEK1 and circCHEK1_246aa induce multiple myeloma cell proliferation, drug resistance, and bone lesion formation
CHEK1 and circCHEK1_246aa evoke myeloma chromosomal instability, partially through CEP170 activation
Abstract
Multiple myeloma (MM) is characterized by clonal expansion of plasma cells in the bone marrow (BM). Therefore, effective therapeutic interventions must target both myeloma cells and the BM niche. In the present study, we first demonstrated that CHEK1 expression was significantly increased in human MM samples relative to normal plasma cells, and that in MM patients, high CHEK1 expression was associated with poor outcomes. CHEK1 overexpression increased cellular proliferation in MM cells and evoked drug resistance in vitro, while CHEK1 knockdown abrogated this effect. Moreover, CHEK1 was a high-risk gene for poor outcome in MM patients, and, in paired samples from MM patients taken from newly diagnosed and relapsed MM, CHEK1 expression was upregulated. CHEK1-mediated increases in cell proliferation and drug resistance were due in part to CHEK1-induced chromosomal instability (CIN), as demonstrated by Giemsa staining, exon sequencing, and immunofluorescence. CHEK1 activated CIN, partly by phosphorylating CEP170. Interestingly, CHEK1 promoted osteoclast differentiation by direct phosphorylation and activation of NFATc1, indicating that CHEK1 inhibition could target both MM cell proliferation and macrophage osteoclast differentiation in the BM niche. Intriguingly, we also discovered that MM cells expressed circCHEK1_246aa, a circular CHEK1 RNA, which encoded and was translated to the CHEK1 kinase catalytic center. Transfection of circCHEK1_246aa increased MM CIN and osteoclast differentiation similarly to CHEK1 overexpression, suggesting that MM cells could secrete circCHEK1_246aa in the BM niche to increase the invasive potential of MM cells and promote osteoclast differentiation. Finally, we demonstrated in vivo in xenograft models that CHEK1 overexpression prompted MM proliferation and drug resistance, while CHEK1 knockdown conversely inhibited MM growth. Together, these findings suggest that targeting the enzymatic catalytic center encoded by CHEK1 mRNA and circCHEK1_246aa is a promising therapeutic modality to target both MM cells and the BM niche.
Figure

Disclosures
No relevant conflicts of interest to declare.
Short Term Exposure Effects of Trichostatin a
Authors: Przychodzen Bart , Smieszek Sandra , Polymeropoulos Christos , Polymeropoulos Mihales 
Published: February 2021

Histone deacetylase inhibitors (HDACi) are small molecules that increase acetylation of lysine residues by ultimately inhibiting the activity of histone deactylase enzymes. These anticancer agents affect epigenetic and non-epigenetic regulation resulting in cell cycle arrest of cancer cell lines. We have conducted high throughput screen to elucidate effect of short term exposure to Trichostatin A on transcriptional activity of a model cell line. We have tested short term exposure (2h) of Trichostatin A (10uM) on ARPE-19 cell line.
In effort to define the molecular signature of TSA we have conducted downstream analyses of transcriptional expression. We have selected genes that showed at least 1.5 fold expression change and were significant (p&lt;0.01). We identified 140 genes that were upregulated and 138 were downregulated. We observe a highly significant enrichment of genes involved dysregulation of p53 pathway (p-value 0.00001). Furthermore we observe a highly significant dysregulation of CREBBP pathway - a protein encoded by this gene has intrinsic histone acetyltransferase activity and also acts as a scaffold to stabilize additional protein interactions with the transcription complex. CREBBP autoacetylation is required for binding to protein substrates, such as acetylated histones and acetylated TP53/p53. KEGG pathways reports aberration of JAK-STAT pathway as well as signaling of Fibroblast Growth Factor Receptor 3 (FGFR3). Using this gene signature further disease perturbation result in a upregulated signature similar to that of Diamond-Blackfan anaemia (p=1.681e-11, OR=8.35). As an independent confirmation we find similar dysregulation patterns as caused by TSA (p=4.8e-86) from other deposited experiments within GEO Omnibus.
These preliminary signatures offer a glance into the transcriptional landscape as elicited by short-term exposure to TSA. Further experiments warrant a more comprehensive observations into the mode of action as well as biomarkers that may be useful to design optimal, TSA-based treatments.

Disclosures
Przychodzen: Vanda Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Smieszek:Vanda Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Polymeropoulos:Vanda Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Polymeropoulos:Vanda Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.
Quantifying the phantom jam externality: the case of an Autobahn section in Germany
Authors: Goldmann Kathrin , Sieg Gernot 
Published: February 2021

AbstractIf not restricted by tolls, private decisions to drive on a highway result in inefficiently high usage which leads to traffic jams. When traffic demand is high, traffic jams can occur simply because of the interaction of vehicle drivers on the road, a phenomenon called phantom jam. The probability of phantom jams occurring increases with traffic flow. Unpriced externalities lead to inefficiently high road usage. We offer a method for quantifying traffic jam externalities and identifying and isolating the phantom jam externality. We examine the method by applying it to a specific highway section in Germany. The maximal congestion externality for the analyzed highway section is about 38 cents per vehicle and kilometer. Congestion charges that are calculated ignoring phantom jam externalities, can only internalize two-thirds of the true externality.
CT differentiation of gastric ectopic pancreas from gastric stromal tumor
Authors: Liu Chang , Yang Fang , Zhang Wenming , Ao Weiqun , An Yongyu , Zhang Cui , Dai Bailing , Pu Cailing , Wang Jian 
Published: February 2021

AbstractBackgroundGastric ectopic pancreas (GEPs) is a rare developmental anomaly which is difficult to differentiate it from submucosal tumor such as gastric stromal tumor (GST) by imaging methods. Since the treatments of the GEPs and GST are totally different, a correct diagnosis is essential. Therefore, we retrospectively investigated the CT features of them to help us deepen the understanding of GEPs and GST.MethodsThis study enrolled 17 GEPs and 119 GST, which were proven pathologically. We assessed clinical and CT features to identify significant differential features of GEPs from GST using univariate and multivariate analyses.ResultsIn univariate analysis, among all clinicoradiologic features, features of age, symptom, tumor marker, location, contour, peritumoral infiltration or fat-line of peritumor, necrosis, calcification, CT attenuation value of unenhancement phase/arterial phase/portal venous phase (CTu/CTa/CTp), the CT attenuation value of arterial phase/portal venous phase minus that of unenhanced phase (DEAP/DEPP), long diameter (LD), short diameter (SD) were considered statistically significant for the differentiation of them. And the multivariate analysis revealed that location, peritumoral infiltration or fat-line of peritumor, necrosis and DEPP were independent factors affecting the identification of them. In addition, ROC analysis showed that the test efficiency of CTp was perfect (AUC = 0.900).ConclusionLocation, the presence of peritumoral infiltration or fat-line of peritumor, necrosis and DEPP are useful CT differentiators of GEPs from GST. In addition, the test efficiency of CTp in differentiating them was perfect (AUC = 0.900).
Genomic and clinical characterisation of multidrug-resistant carbapenemase-producing ST231 and ST16 Klebsiella pneumoniae isolates colonising patients at Siriraj hospital, Bangkok, Thailand from 2015 to 2017
Authors: Boonyasiri Adhiratha , Jauneikaite Elita , Brinkac Lauren M. , Greco Chris , Lerdlamyong Kanokorn , Tangkoskul Teerawit , Nguyen Kevin , Thamlikitkul Visanu , Fouts Derrick E. 
Published: February 2021

Abstract
Background
Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data.

Methods
The clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were “colonised” or “infected” with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes.

Results
Altogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae. The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was blaOXA-232, with blaNDM-1 additionally identified in 19 of them. All CPE isolates carrying either blaOXA-232 or blaNDM-1 were resistant to meropenem, but only 40 from 45 were susceptible to colistin. Among the CPE-infected patients (n = 18) and CPE-colonised patients who developed CPE infections during the study (n = 3), all but one received standard colistin-based combination therapy. Phylogenetic analysis revealed the polyclonal spread of carbapenemase-producing K. pneumoniae (CPKP) within the patient population, with the following two major subclades identified: ST16 (n = 15) and ST231 (n = 14). CPKP-ST231 had the highest virulence score of 4 and was associated with primary bacteraemia. The siderophores yersiniabactin and aerobactin, considered to be important virulence factors, were only identified in the CPKP-ST231 genomes.

Conclusions
This study has revealed the genomic features of colonising CPE isolates, focusing on antimicrobial resistance and virulence determinants. This type of multi-layered analysis can be further exploited in Thailand and elsewhere to modify the regimes used for empirical antibiotic treatment and improve the management strategies for CPE infections in hospitalised patients.
Long non-coding RNA H19 expression and functional polymorphism rs217727 are linked to increased ischemic stroke risk
Authors: Rezaei Mohadese , Mokhtari Mohammad Javad , Bayat Mahnaz , Safari Anahid , Dianatpuor Mehdi , Tabrizi Reza , Asadabadi Tahereh , Borhani-Haghighi Afshin 
Published: February 2021

Abstract
Background
Efforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable. The H19 gene plays a functional role in increasing the prevalence of IS risk factors. We evaluated the correlation between H19 rs217727 polymorphism and the expression level of H19 lncRNA with susceptibility to IS among the Iranian population.

Methods
Blood samples were collected from IS patients (n = 114) and controls (n = 114). We concentrated on the expression pattern of H19 at different time points (i.e., 0–24, 24–48, and 48–72 h after stroke). The tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method was applied for DNA genotyping. We used the quantitative real-time PCR to evaluate H19 expression levels. We used the receiver operating characteristic (ROC) curve to evaluate the diagnosis and prognosis of IS.

Results
The rs217727polymorphism of H19 was related with IS susceptibility in the co-dominant (OR = 2.92, 95% CI = 0.91–10.92, P = 0.04) and recessive models (OR = 2.80, 95% CI = 0.96–8.15, P = 0.04). H19 expression was significantly upregulated in IS and remained high for 72 h after stroke. ROC curves showed that H19 expression within the first 24 h from stroke onset might serve as a biomarker for the early diagnosis of IS with 79.49% sensitivity and 80.00% specificity. H19 expression in small vessel occlusion (SVO) and large-artery atherosclerosis (LAA) patients were 3.74 and 3.34 times higher than the undetermined (UD) subtype, respectively [OR = 3.74 95% CL (1.14–12.27) P = 0.030 and OR = 3.34 95% CL (1.13–9.85) P = 0.029].

Conclusion
The rs217727 polymorphism of the H19 is correlated with IS susceptibility, and H19 expression levels were higher in SVO and LAA patients. The upregulation of H19 may be considered as a diagnostic biomarker in IS among the Iranian population, but it cannot serve as a useful prognostic marker.
Efficacy of extracranial stereotactic body radiation therapy (SBRT) added to standard treatment in patients with solid tumors (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases: study protocol for a randomised phase III trial (STEREO-OS)
Authors: Thureau Sébastien , Marchesi Vincent , Vieillard Marie-Hélène , Perrier Lionel , Lisbona Albert , Leheurteur Marianne , Tredaniel Jean , Culine Stéphane , Dubray Bernard , Bonnet Naïma , Asselain Bernard , Salleron Julia , Faivre Jean-Christophe 
Published: February 2021

Abstract
Background
Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone.

Methods
This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment.
For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years.
The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis.

Discussion
The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts.

Trials registration
ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing study
Telehealth sounds a bit challenging, but it has potential: participant and physiotherapist experiences of gym-based exercise intervention for Achilles tendinopathy monitored via telehealth
Authors: Hasani F. , Malliaras P. , Haines T. , Munteanu S. E. , White J. , Ridgway J. , Nicklen P. , Moran A. , Jansons P. 
Published: February 2021

Abstract
Background
Although telehealth is becoming more popular for delivery of care for individuals with musculoskeletal pain, to our knowledge telehealth has not been used to manage Achilles tendinopathy. This research aimed to explore the experience of participants and physiotherapists with gym-based exercise interventions for Achilles tendinopathy monitored via videoconference.

Methods
A qualitative, interpretive description design was performed using semi-structured interviews (8 participants) and a focus group (7 physiotherapists). Participants and physiotherapists were interviewed about their experiences of the use of telehealth during a gym-based exercise intervention incorporating different calf load parameters for Achilles tendinopathy. We employed an inductive thematic analysis approach to analyse the data.

Results
Three themes identified from both participants and physiotherapists included i) acceptability of telehealth; ii) enablers to adherence with telehealth; and iii) barriers to adherence with telehealth. Two extra themes arose from participants regarding adherence with gym-based exercise, including enablers to adherence with the exercise intervention, and barriers to adherence with the exercise intervention. Both participants and physiotherapists expressed overall satisfaction and acceptability of telehealth monitoring of gym-based exercise.

Conclusion
Gym-based exercise intervention for Achilles tendinopathy involving weekly telehealth monitoring was acceptable to both participants and physiotherapists. Potential enablers and barriers were identified that may improve adherence to this type of intervention.
Transient light-activated gene expression in Chinese hamster ovary cells
Authors: Minami Shiaki A. , Shah Priya S. 
Published: February 2021

Abstract
Background
Chinese hamster ovary (CHO) cells are widely used for industrial production of biopharmaceuticals. Many genetic, chemical, and environmental approaches have been developed to modulate cellular pathways to improve titers. However, these methods are often irreversible or have off-target effects. Development of techniques which are precise, tunable, and reversible will facilitate temporal regulation of target pathways to maximize titers. In this study, we investigate the use of optogenetics in CHO cells. The light-activated CRISPR-dCas9 effector (LACE) system was first transiently transfected to express eGFP in a light-inducible manner. Then, a stable system was tested using lentiviral transduction.

Results
Transient transfections resulted in increasing eGFP expression as a function of LED intensity, and activation for 48 h yielded up to 4-fold increased eGFP expression compared to cells kept in the dark. Fluorescence decreased once the LACE system was deactivated, and a protein half-life of 14.9 h was calculated, which is in agreement with values reported in the literature. In cells stably expressing the LACE system, eGFP expression was confirmed, but there was no significant increase in expression following light activation.

Conclusions
Taken together, these results suggest that optogenetics can regulate CHO cell cultures, but development of stable cell lines requires optimized expression levels of the LACE components to maintain high dynamic range.