bluuebunny/crossref_metadata_2025_split huggingface dataset:
Entry and exit of chemotherapeutically-promoted cellular dormancy in glioblastoma cells is differentially affected by the chemokines CXCL12, CXCL16, and CX3CL1
Authors: Adamski Vivian , Hattermann Kirsten , Kubelt Carolin , Cohrs Gesa , Lucius Ralph , Synowitz Michael , Sebens Susanne , Held-Feindt Janka 
Published: April 2020

AbstractGlioblastoma multiforme (GBM) is a malignant brain tumor that evades therapy regimens. Since cellular dormancy is one strategy for surviving, and since chemokines determine the environmental conditions in which dormancy occurs, we investigated how chemokines affect temozolomide (TMZ)-promoted cellular dormancy entry and exit in GBM cells. TMZ administration over ten days promoted cellular dormancy entry, whereas discontinuing TMZ for a further 15 days resulted in resumption of proliferation. Co-administration of a chemokine cocktail containing CXCL12, CXCL16, and CX3CL1 resulted in both delayed entry and exit from cellular dormancy. A microarray-based transcriptome analysis in LN229 GBM cells revealed that cellular dormancy entry was characterized by an increased expression of CCL2 and SAA2, while THSD4, FSTL3, and VEGFC were upregulated during dormancy exit. Co-stimulation with the chemokine cocktail reduced upregulation of identified genes. After verifying the appearance of identified genes in human GBM primary cultures and ex vivo samples, we clarified whether each chemokine alone impacts cellular dormancy mechanisms using specific antagonists and selective CRISPR/Cas9 clones. While expression of CCL2 and SAA2 in LN229 cells was altered by the CXCL12-CXCR4-CXCR7 axis, CXCL16 and CX3CL1 contributed to reduced upregulation of THSD4 and, to a weaker extent, of VEGFC. The influence on FSTL3 expression depended on the entire chemokine cocktail. Effects of chemokines on dormancy entry and exit-associated genes were detectable in human GBM primary cells, too, even if in a more complex, cell-specific manner. Thus, chemokines play a significant role in the regulation of TMZ-promoted cellular dormancy in GBMs.
A novel role of LRP5 in tubulointerstitial fibrosis through activating TGF-β/Smad signaling
Authors: He Xuemin , Cheng Rui , Huang Chao , Takahashi Yusuke , Yang Yanhui , Benyajati Siribhinya , Chen Yanming , Zhang Xin A. , Ma Jian-xing 
Published: April 2020

AbstractPrevious studies by us and others demonstrated that activation of Wnt/β-catenin signaling plays a pathogenic role in chronic kidney diseases (CKD). Wnt co-receptor LRP5 variants are reported to associate with autosomal dominant polycystic kidney disease; but their exact roles in this disease and renal fibrosis have not been explored. Here, we observed the upregulation of LRP5 in the renal tubules of both type 1 and type 2 diabetic models and of an obstructive nephropathy model. In the obstructed kidneys, Lrp5 knockout significantly ameliorated tubulointerstitial fibrosis and tubular injury without changing Wnt/β-catenin signaling. Instead, decreased levels of TGF-β1 and TGF-β receptors (TβRs) were detected in Lrp5 knockout kidneys, followed by attenuated activation and nuclear translocation of Smad2/3 in the renal tubules, suggesting a regulatory effect of LRP5 on TGF-β/Smad signaling. In consistent with this hypothesis, LRP5 overexpression resulted in enhanced TGF-β/Smad signaling activation in renal tubule epithelial cells. Furthermore, LRP5 was co-immunoprecipitated with TβRI and TβRII, and its extracellular domain was essential for interacting with TβRs and for its pro-fibrotic activity. In addition to stabilizing TβRs, LRP5 increased the basal membrane presentation and TGF-β1-induced internalization of these receptors. Notably, TGF-β1 also induced LRP5 internalization. These findings indicate that LRP5 promotes tubulointerstitial fibrosis, at least partially, via direct modulation of TGF-β/Smad signaling, a novel, Wnt-independent function.
Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL)
Authors: Gelsomino Francesco , Tiseo Marcello , Barbieri Fausto , Riccardi Ferdinando , Cavanna Luigi , Frassoldati Antonio , Delmonte Angelo , Longo Lucia , Dazzi Claudio , Cinieri Saverio , Colantonio Ida , Sperandi Francesca , Lamberti Giuseppe , Brocchi Stefano , Tofani Lorenzo , Boni Luca , Ardizzoni Andrea 
Published: April 2020

Abstract
Background
Despite sensitivity to first-line chemotherapy, most small-cell lung cancer (SCLC) patients relapse. In this setting, topotecan demonstrated modest activity with significant toxicity. Paclitaxel was also active. This study was designed to evaluate activity and safety of nab-paclitaxel in relapsed SCLC.

Methods
In this multicentre prospective Phase 2 trial, patients with refractory or sensitive SCLC progressed to first-line platinum-based chemotherapy received nab-paclitaxel 100 mg/smq on days 1, 8, 15 every 4 weeks up to six cycles, progressive disease or intolerable toxicity. Primary endpoint was investigator-assessed objective tumour response. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).

Results
Of the 68 patients treated, partial response was 8% in the refractory cohort and 14% in the sensitive cohort. Most common toxicities of any grade were fatigue (54%), anaemia (38%), neutropenia (29%), leukopenia (26%) and diarrhoea (21%). Median PFS was similar in both refractory (1.8 months) and sensitive cohorts (1.9 months), while median OS was longer in sensitive one (6.6 versus 3.6 months).

Conclusions
Although nab-paclitaxel has shown some modest anti-tumour activity in relapsed SCLC, associated with a favourable toxicity profile, the primary end-point of the study was not met.

Clinical Trial registration
Clinical Trial registration number is ClinicalTrials.gov Identifier: NCT03219762.
JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction
Authors: Simula Luca , Corrado Mauro , Accordi Benedetta , Di Rita Anthea , Nazio Francesca , Antonucci Ylenia , Di Daniele Arianna , Caicci Federico , Caruana Ignazio , Soriano Maria Eugenia , Pigazzi Martina , Locatelli Franco , Cecconi Francesco , Campello Silvia 
Published: April 2020

AbstractThe Activation-Induced Cell Death (AICD) is a stimulation-dependent form of apoptosis used by the organism to shutdown T-cell response once the source of inflammation has been eliminated, while allowing the generation of immune memory. AICD is thought to progress through the activation of the extrinsic Fas/FasL pathway of cell death, leading to cytochrome-C release through caspase-8 and Bid activation. We recently described that, early upon AICD induction, mitochondria undergo structural alterations, which are required to promote cytochrome-C release and execute cell death. Here, we found that such alterations do not depend on the Fas/FasL pathway, which is instead only lately activated to amplify the cell death cascade. Instead, such alterations are primarily dependent on the MAPK proteins JNK1 and ERK1/2, which, in turn, regulate the activity of the pro-fission protein Drp1 and the pro-apoptotic factor Bim. The latter regulates cristae disassembly and cooperate with Drp1 to mediate the Mitochondrial Outer Membrane Permeabilization (MOMP), leading to cytochrome-C release. Interestingly, we found that Bim is also downregulated in T-cell Acute Lymphoblastic Leukemia (T-ALL) cells, this alteration favouring their escape from AICD-mediated control.
Chk1-mediated phosphorylation of Cdh1 promotes the SCFβTRCP-dependent degradation of Cdh1 during S-phase and efficient cell-cycle progression
Authors: Pal Debjani , Torres Adrian E. , Stromberg Benjamin R. , Messina Abbey L. , Dickson Andrew S. , De Kuntal , Willard Belinda , Venere Monica , Summers Matthew K. 
Published: April 2020

AbstractAPC/CCdh1 is a ubiquitin ligase with roles in numerous diverse processes, including control of cellular proliferation and multiple aspects of the DNA damage response. Precise regulation of APC/CCdh1 activity is central to efficient cell-cycle progression and cellular homeostasis. Here, we have identified Cdh1 as a direct substrate of the replication stress checkpoint effector kinase Chk1 and demonstrate that Chk1-mediated phosphorylation of Cdh1 contributes to its recognition by the SCFβTRCP ubiquitin ligase, promotes efficient S-phase entry, and is important for cellular proliferation during otherwise unperturbed cell cycles. We also find that prolonged Chk1 activity in late S/G2 inhibits Cdh1 accumulation. In addition to promoting control of APC/CCdh1 activity by facilitating Cdh1 destruction, we find that Chk1 also antagonizes activity of the ligase by perturbing the interaction between Cdh1 and the APC/C. Overall, these data suggest that the rise and fall of Chk1 activity contributes to the regulation of APC/CCdh1 activity that enhances the replication process.
Restoration of leg length and offset correlates with trochanteric pain syndrome in total hip arthroplasty
Authors: Worlicek Michael , Messmer Benedikt , Grifka Joachim , Renkawitz Tobias , Weber Markus 
Published: April 2020

AbstractPersistent pain around the greater trochanter is a common complication after total hip arthroplasty. Restoration of biomechanics such as leg length, femoral und acetabular offset is crucial in THA. The purpose of this study was to evaluate postoperative differences of these parameters after THA and to analyze their association to greater trochanteric pain syndrome. Furthermore, we aimed to evaluate the clinical relevance of trochanteric pain syndrome compared to patient reported outcome measures. 3D-CT scans of 90 patients were analyzed after minimalinvasive total hip arthroplasty and leg length, femoral and acetabular offset differences were measured. Clinical evaluation was performed three years after THA regarding the presence of trochanteric pain syndrome and using outcome measures. Furthermore, the patients’ expectation were evaluated. Patients with trochanteric pain syndrome showed a higher absolute discrepancy of combined leg length, femoral and acetabular offset restoration compared to the non-operated contralateral side with 11.8 ± 6.0 mm than patients without symptoms in the trochanteric region with 7.8 ± 5.3 mm (p = 0.01). Patients with an absolute deviation of the combined parameters of more than 5 mm complained more frequently about trochanteric symptoms (29.2%, 19/65) than patients with a biomechanical restoration within 5 mm compared to the non-affected contralateral side (8.0%, 2/25, p = 0.03). Clinical outcome measured three years after THA was significantly lower in patients with trochanteric symptoms than without trochanteric pain (p < 0.03). Similarly, fulfillment of patient expectations as measured by THR-Survey was lower in the patients with trochanteric pain (p < 0.005). An exact combined restoration of leg length, acetabular and femoral offset reduces significantly postoperative trochanteric pain syndrome and improves the clinical outcome of the patients.
Investigating APOE, APP-Aβ metabolism genes and Alzheimer’s disease GWAS hits in brain small vessel ischemic disease
Authors: Blumenau Sonja , Foddis Marco , Müller Susanne , Holtgrewe Manuel , Bentele Kajetan , Berchtold Daniel , Beule Dieter , Dirnagl Ulrich , Sassi Celeste 
Published: April 2020

AbstractAlzheimer’s disease and small vessel ischemic disease frequently co-exist in the aging brain. However, pathogenic links between these 2 disorders are yet to be identified. Therefore we used Taqman genotyping, exome and RNA sequencing to investigate Alzheimer’s disease known pathogenic variants and pathways: APOE ε4 allele, APP-Aβ metabolism and late-onset Alzheimer’s disease main genome-wide association loci (APOE, BIN1, CD33, MS4A6A, CD2AP, PICALM, CLU, CR1, EPHA1, ABCA7) in 96 early-onset small vessel ischemic disease Caucasian patients and 368 elderly neuropathologically proven controls (HEX database) and in a mouse model of cerebral hypoperfusion. Only a minority of patients (29%) carried APOE ε4 allele. We did not detect any pathogenic mutation in APP, PSEN1 and PSEN2 and report a burden of truncating mutations in APP-Aß degradation genes. The single-variant association test identified 3 common variants with a likely protective effect on small vessel ischemic disease (0.54>OR > 0.32, adj. p-value <0.05) (EPHA1 p.M900V and p.V160A and CD33 p.A14V). Moreover, 5/17 APP-Aß catabolism genes were significantly upregulated (LogFC > 1, adj. p-val<0.05) together with Apoe, Ms4a cluster and Cd33 during brain hypoperfusion and their overexpression correlated with the ischemic lesion size. Finally, the detection of Aβ oligomers in the hypoperfused hippocampus supported the link between brain ischemia and Alzheimer’s disease pathology.
High-order mode suppression in double-clad optical fibers by adding absorbing inclusions
Authors: Aleshkina Svetlana S. , Kochergina Tatiana A. , Velmiskin Vladimir V. , Bobkov Konstantin K. , Bubnov Mikhail M. , Yashkov Mikhail V. , Lipatov Denis S. , Salganskii Mikhail Yu. , Guryanov Alexey N. , Likhachev Mikhail E. 
Published: April 2020

AbstractWe proposed and experimentally demonstrated a technique for the suppression of unwanted modes in double-clad fibers with a high core-to-clad diameter ratio by introducing high-index absorbing inclusions into the first cladding of the fibers. These inclusions disturb the shape of undesirable modes, and a noticeable part of the power becomes localized inside the inclusion, resulting in an increase in the propagation loss of these modes. Two fiber designs were studied and realized: one with cylindrical symmetry and an absorbing high-index ring as the inclusion and another with high-index absorbing rods inserted around the fiber core. In both cases, the possibility of achieving perfect single-mode propagation was demonstrated both theoretically and experimentally.
Optimization of Ultra-High-Performance Liquid Chromatography-Electrospray Ionization-Mass Spectrometry Detection of Glutamine-FMOC Ad-Hoc Derivative by Central Composite Design
Authors: Bheemanapally Khaggeswar , Ibrahim Mostafa M. H. , Briski Karen P. 
Published: April 2020

AbstractGlutamine (Gln) is converted to excitatory (glutamate, aspartate) and inhibitory (γ-amino butyric acid) amino acid neurotransmitters in brain, and is a source of energy during glucose deprivation. Current research utilized an Analytical Quality by Design approach to optimize levels and combinations of critical gas pressure (sheath, auxiliary, sweep) and temperature (ion transfer tube, vaporizer) parameters for high-sensitivity mass spectrometric quantification of brain tissue glutamine. A Design of Experiments (DOE) matrix for evaluation of relationships between these multiple independent variables and a singular response variable, e.g. glutamine chromatogram area, was developed by statistical response surface methodology using central composite design. A second-order polynomial equation was generated to identify and predict singular versus combinatory effects of synergistic and antagonistic factors on chromatograph area. Predicted versus found outcomes overlapped, with enhanced area associated with the latter. DOE methodology was subsequently used to evaluate liquid chromatographic variable effects, e.g. flow rate, column temperature, and mobile phase composition on the response variable. Results demonstrate that combinatory AQbD-guided mass spectrometric/liquid chromatographic optimization significantly enhanced analytical sensitivity for Gln, thus enabling down-sized brain tissue sample volume procurement for quantification of this critical amino acid.
Materials and Device Considerations in Electrophoretic Drug Delivery Devices
Authors: Chen Shao-Tuan , Proctor Christopher M. , Malliaras George G. 
Published: April 2020

AbstractElectrophoretic drug delivery devices are able to deliver drugs with exceptional temporal and spatial precision. This technology has emerged as a promising platform for treating pathologies ranging from neuropathic pain to epilepsy. As the range of applications continues to expand, there is an urgent need to understand the underlying physics and estimate materials and device parameters for optimal performance. Here, computational modeling of the electrophoretic drug delivery device is carried out. Three critical performance indices, namely, the amount of drug transported, the pumping efficiency and the ON/OFF ratio are investigated as a function of initial drug concentration in the device and fixed charge concentration in the ion exchange membrane. The results provide guidelines for future materials and device design with an eye towards tailoring device performance to match disease-specific demands.
Ly6cLo non-classical monocytes promote resolution of rhesus rotavirus-mediated perinatal hepatic inflammation
Authors: Alkhani Anas , Levy Claire S. , Tsui Margaret , Rosenberg Katherine A. , Polovina Katya , Mattis Aras N. , Mack Matthias , Van Dyken Steven , Wang Bruce M. , Maher Jacquelyn J. , Nijagal Amar 
Published: April 2020

AbstractPerinatal hepatic inflammation can have devastating consequences. Monocytes play an important role in the initiation and resolution of inflammation, and their diverse functions can be attributed to specific cellular subsets: pro-inflammatory or classical monocytes (Ly6cHi) and pro-reparative or non-classical monocytes (Ly6cLo). We hypothesized that inherent differences in Ly6cHi classical monocytes and Ly6cLo non-classical monocytes determine susceptibility to perinatal hepatic inflammation in late gestation fetuses and neonates. We found an anti-inflammatory transcriptional profile expressed by Ly6cLo non-classical monocytes, and a physiologic abundance of these cells in the late gestation fetal liver. Unlike neonatal pups, late gestation fetuses proved to be resistant to rhesus rotavirus (RRV) mediated liver inflammation. Furthermore, neonatal pups were rendered resistant to RRV-mediated liver injury when Ly6cLo non-classical monocytes were expanded. Pharmacologic inhibition of Ly6cLo non-classical monocytes in this setting restored susceptibility to RRV-mediated disease. These data demonstrate that Ly6cLo monocytes promote resolution of perinatal liver inflammation in the late gestation fetus, where there is a physiologic expansion of non-classical monocytes, and in the neonatal liver upon experimental expansion of these cells. Therapeutic strategies directed towards enhancing Ly6cLo non-classical monocyte function may mitigate the detrimental effects of perinatal liver inflammation.
The unexpected effect of aqueous ion pairs on the forbidden n → π* transition in nitrate
Authors: Pedersen Pernille D. , Mikkelsen Kurt V. , Johnson Matthew S. 
Published: April 2020

Computational results suggest that significant differences in the optical properties of nitrate ion pairs could explain the experimentally observed salt-specific effect of adding different salts to a solution of KNO3 on the n→π* absorption.
Does the Inclusion of a Genome-Wide Polygenic Score Improve Early Risk Prediction for Later Language and Literacy Delay?
Authors: Dale Philip S. , von Stumm Sophie , Selzam Saskia , Hayiou-Thomas Marianna E. 
Published: April 2020

Purpose
The ability to identify children early in development who are at substantial risk for language/literacy difficulties would have great benefit both for the children and for the educational and therapeutic institutions that serve them. Information that is relatively easily available prior to the age of 3 years, such as late talking, family history of language/literacy difficulties, and socioeconomic status, have some but very limited predictive power. Here, we examine whether the inclusion of a DNA-based genome-wide polygenic score that has been shown to capture children's genetic propensity for educational attainment (EA3) adds enough prediction to yield a clinically useful score.

Method
Data are longitudinal scores of 1,420 children from the Twins Early Development Study, who were assessed at ages 2 and 3 years on language and nonverbal ability and at 12 years of age on oral language, word decoding, and reading comprehension. Five risk factors were examined: expressive vocabulary, nonverbal ability (these two from parent report), family history, mothers' education, and EA3. Analyses were conducted both for continuous and categorically defined measures of risk and outcome.

Results
Language and literacy abilities at 12 years of age were significantly but modestly predicted by the risk factors, with a small but significant added prediction from EA3. Indices of diagnostic validity for poor outcomes, such as sensitivity and area under the curve statistics, were poor in all cases.

Conclusions
We conclude that, at present, clinically useful prediction from toddlerhood remains an unattained goal.

Supplemental Material

https://doi.org/10.23641/asha.12170331
Hierarchical quantitative analysis to evaluate unsafe driving behaviour from massive trajectory data
Authors: Liao Lyuchao , Chen Bijun , Zou Fumin , Eben Li Shengbo , Liu Jierui , Wu Xinke , Dong Ni 
Published: April 2020

The large‐scale trajectory data provide the potential opportunity to a better understanding of driving behaviour for transportation applications and research. However, limited effort has been paid to the study on the evaluation of unsafe driving behaviour (UDB) based on trajectory data. In this work, the authors propose a four‐layer processing framework for evaluation of driving behaviour using trajectory data, and first analyse the statistical distribution of various factors and mine UDBs from trajectory data by measuring the deviation from a normal distribution. Then, a membership function is designed to evaluate the severity rating of UDBs, and finally, an analytical hierarchy process‐based method is employed to analyse UDBs both qualitatively and quantitatively. With experiments on trajectory data derived from August to September 2018 in Jiangxi, China, vehicles were classified in levels of risk, and the result shows that the proposed method offers a feasible and applicable way for transportation enterprises and drivers to monitor driving behaviour in real‐time.
Rotational relaxation of H2S by collision with He
Authors: Denis-Alpizar Otoniel , Stoecklin Thierry 
Published: April 2020

Context. The H2S molecule has been detected in several regions of the interstellar medium (ISM). The use of non-LTE models requires knowledge of accurate collisional rate coefficients of the molecules detected with the most common collider in the ISM.
Aims. The main goal of this work is to study the collision of H2S with He.
Methods. A grid of ab initio energies was computed at the coupled cluster level of theory including single, double, and perturbative triple excitations (CCSD(T)) and using the augmented correlation consistent polarized quadruple zeta (aug-cc-pVQZ) basis set supplemented by a set of mid-bond functions. These energies were fitted to an analytical function, which was employed to study the dynamics of the system. Close coupling calculations were performed to study the collision of H2S with He.
Results. The rate coefficients determined from the close coupling calculation were compared with those of the collision with H2O+He, and large differences were found. Finally, the rate coefficients for the lower rotational de-excitation of H2S by collision with He are reported.
La Littérature, stéthoscope du monde
Authors: Antoine-Meyzonnade Marie-Hélène 
Published: April 2020

Que la littérature soit en relation avec l’écoute, c’est une évidence. Mais d’abord pour l’écoute du lecteur; il faut aller jusqu’à celle de l’écrivain qui, selon l’étymologie du mot, tend l’oreille au monde, quel qu’il soit.
Le monde et l’homme sont faits de langage – à écouter, à déchiffrer et à rendre le mieux possible dans sa propre langue.
L’écrivain écoute, et la littérature reflète cette écoute.