bluuebunny/crossref_metadata_2025_split huggingface dataset:
New insights into ion channel‐dependent signalling during left‐right patterning
Authors: Tajhya Rajeev , Delling Markus 
Published: May 2019

AbstractThe left‐right organizer (LRO) in the mouse consists of pit cells within the depression, located at the end of the developing notochord, also known as the embryonic node and crown cells lining the outer periphery of the node. Cilia on pit cells are posteriorly tilted, rotate clockwise and generate leftward fluid flow. Primary cilia on crown cells are required to interpret the directionality of fluid movement and initiate flow‐dependent gene transcription. Crown cells express PC1‐L1 and PC2, which may form a heteromeric polycystin channel complex on primary cilia. It is still only poorly understood how fluid flow activates the ciliary polycystin complex. Besides polycystin channels voltage gated channels like HCN4 and KCNQ1 have been implicated in establishing asymmetry. How this electrical network of ion channels initiates left‐sided signalling cascades and differential gene expression is currently only poorly defined.
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Vibrations of an Incompressible Linearly Elastic Plate Using Discontinuous Finite Element Basis Functions for Pressure
Authors: Yuan Lisha , Batra Romesh C. 
Published: May 2019

Abstract
We numerically analyze, with the finite element method, free vibrations of incompressible rectangular plates under different boundary conditions with a third-order shear and normal deformable theory (TSNDT) derived by Batra. The displacements are taken as unknowns at the nodes of a 9-node quadrilateral element and the hydrostatic pressure at four interior nodes. The plate theory satisfies the incompressibility condition, and the basis functions satisfy the Babuska-Brezzi condition. Because of the singular mass matrix, Moler's QZ algorithm (also known as the generalized Schur decomposition) is used to solve the resulting eigenvalue problem. Computed results for simply supported, clamped, and clamped-free rectangular isotropic plates agree well with the corresponding analytical frequencies of simply supported plates and with those found using the commercial software, abaqus, for other edge conditions. In-plane modes of vibrations are clearly discerned from mode shapes of square plates of aspect ratio 1/8 for all three boundary conditions. The magnitude of the transverse normal strain at a point is found to equal the sum of the two axial strains implying that higher-order plate theories that assume null transverse normal strain will very likely not provide good solutions for plates made of rubberlike materials that are generally taken to be incompressible. We have also compared the presently computed through-the-thickness distributions of stresses and the hydrostatic pressure with those found using abaqus.
Epidemiological Transition in Physical Activity and Sedentary Time in Children
Authors: Barreira Tiago V. , Broyles Stephanie T. , Tudor-Locke Catrine , Chaput Jean-Philippe , Fogelholm Mikael , Hu Gang , Kuriyan Rebecca , Lambert Estelle V. , Maher Carol A. , Maia José A. , Olds Timothy , Onywera Vincent , Sarmiento Olga L. , Standage Martyn , Tremblay Mark S. , Katzmarzyk Peter T. , _ _ 
Published: May 2019

Background: To determine if children’s moderate to vigorous physical activity (MVPA) and sedentary time varied across levels of household income in countries at different levels of Human Development Index (HDI), consistent with the theory of epidemiological transition. Methods: Data from 6548 children (55% girls) aged 9–11 years from 12 countries at different HDI levels are used in this analysis to assess MVPA and sedentary time (measured using ActiGraph accelerometers) across levels of household income. Least-square means are estimated separately for boys and girls at the estimated 10th, 50th, and 90th percentiles of HDI for the sample. Results: For boys, time in MVPA is negatively associated with income at the 10th and 50th percentiles of HDI (both P < .002). For girls, time in MVPA is negatively associated with income at the 10th and 50th percentiles of HDI (all P < .01) and positively related with income at the 90th percentile (P = .04). Sedentary time is positively associated with income at the 10th percentile of HDI for boys (P = .03), but not for girls. Conclusions: Results support the possibility of an epidemiological transition in physical activity, with lower levels of MVPA observed at opposite levels of income depending on the HDI percentile. This phenomenon was not observed for sedentary time.
Treatment of patients with relapsed or refractory CD19+ lymphoid disease with T lymphocytes transduced by RV-SFG.CD19.CD28.4-1BBzeta retroviral vector: a unicentre phase I/II clinical trial protocol
Authors: Schubert Maria-Luisa , Schmitt Anita , Sellner Leopold , Neuber Brigitte , Kunz Joachim , Wuchter Patrick , Kunz Alexander , Gern Ulrike , Michels Birgit , Hofmann Susanne , Hückelhoven-Krauss Angela , Kulozik Andreas , Ho Anthony D. , Müller-Tidow Carsten , Dreger Peter , Schmitt Michael 
Published: May 2019

IntroductionChimeric antigen receptor (CAR) T cells spark hope for patients with CD19+ B cell neoplasia, including relapsed or refractory (r/r) acute lymphoblastic leukaemia (ALL) or r/r non-Hodgkin’s lymphoma (NHL). Published studies have mostly used second-generation CARs with 4-1BB or CD28 as costimulatory domains. Preclinical results of third-generation CARs incorporating both elements have shown superiority concerning longevity and proliferation. The University Hospital of Heidelberg is the first institution to run an investigator-initiated trial (IIT) CAR T cell trial (Heidelberg Chimeric Antigen Receptor T cell Trial number 1 [HD-CAR-1]) in Germany with third-generation CD19-directed CAR T cells.Methods and analysisAdult patients with r/r ALL (stratum I), r/r NHL including chronic lymphocytic leukaemia, diffuse large B-cell lymphoma, follicular lymphoma or mantle cell lymphoma (stratum II) as well as paediatric patients with r/r ALL (stratum III) will be treated with autologous T-lymphocytes transduced by third-generation RV-SFG.CD19.CD28.4-1BB zeta retroviral vector (CD19.CAR T cells). The main purpose of this study is to evaluate safety and feasibility of escalating CD19.CAR T cell doses (1–20×106transduced cells/m2) after lymphodepletion with fludarabine (flu) and cyclophosphamide (cyc). Patients will be monitored for cytokine release syndrome (CRS), neurotoxicity, i.e. CAR-T-cell-related encephalopathy syndrome (CRES) and/or other toxicities (primary objectives). Secondary objectives include evaluation ofin vivofunction and survival of CD19.CAR T cells and assessment of CD19.CAR T cell antitumour efficacy.HD-CAR-1 as a prospective, monocentric trial aims to make CAR T cell therapy accessible to patients in Europe. Currently, HD-CAR-1 is the first and only CAR T cell IIT in Germany. A third-generation Good Manufacturing Practice (GMP) grade retroviral vector, a broad spectrum of NHL, treatment of paediatric and adult ALL patients and inclusion of patients even after allogeneic stem cell transplantation (alloSCT) make this trial unique.Ethics and disseminationEthical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings.Trial registration numberEudra CT 2016-004808-60;NCT03676504; Pre-results.
Comparison of the activity of selamectin, imidacloprid and fipronil for the treatment of dogs infested experimentally withCtenocephalldes canisandCtenocephalides felis felis
Authors: Cadiergues M. C. , Caubet C. , Franc M. 
Published: May 2019

Twenty‐four beagles were randomly allocated into four groups of six and housed in separate cages. Each dog was infested with 25Ctenocephalides canisand 25Ctenocephalides felis felisand two days later (day 0) the dogs in groups 1, 2 and 3 received a spot‐on application of selamectin (6 mg/kg), imidacloprid (10 mg/kg), or fipronil (6.7 mg/kg), respectively, while the dogs in group 4 were not treated. The dogs were combed 48 hours later, the fleas were removed, counted and their species were determined. All the dogs were reinfested with the same number of the two species of fleas on days 7,14,21,28 and 35, and the efficacy of the treatments was calculated 48 hours after each infestation. The mean numbers of fleas on the control dogs were 19.8C canisand 14.7C felis felis. The three treatments were effective for the full 35 days of the trial; over the first 28 days, the efficacy of selamectin ranged from 81 to 100 and 92 to 99 per cent againstC felis felisandC canis, respectively, the efficacy of imidacloprid ranged from 98 to 100 per cent and the efficacy of fipronil was 100 per cent against both species. There were no significant differences between the three treatments.
Promises and Pitfalls of Using Liquid Biopsy for Precision Medicine
Authors: Rossi Giovanna , Ignatiadis Michail 
Published: May 2019

AbstractNew sensitive assays are currently available for the detection of circulating tumor DNA (ctDNA) and circulating tumor cells (CTC). However, there remains a need for standardization of preanalytical issues and cross-platform comparison studies. Liquid biopsies are being evaluated for treatment selection, for monitoring disease response and resistance, for tracking minimal residual disease, and for cancer diagnosis. Multiple studies are underway to assess the clinical utility of CTC and ctDNA in different settings (treatment-naïve vs. resistant, adjuvant vs. metastatic) and for different treatment modalities (systemic therapy, surgery, radiation therapy). This review aims to map the challenges that remain to be addressed before liquid biopsies can be widely used for cancer management.
Identification of TP53RK-Binding Protein (TPRKB) Dependency in TP53-Deficient Cancers
Authors: Goswami Moloy T. , VanDenBerg Kelly R. , Han Sumin , Wang Lei Lucy , Singh Bhavneet , Weiss Travis , Barlow Myles , Kamberov Steven , Wilder-Romans Kari , Rhodes Daniel R. , Feng Felix Y. , Tomlins Scott A. 
Published: May 2019

Abstract

Tumor protein 53 (TP53; p53) is the most frequently altered gene in human cancer. Identification of vulnerabilities imposed by TP53 alterations may enable effective therapeutic approaches. Through analyzing short hairpin RNA (shRNA) screening data, we identified TP53RK-Binding Protein (TPRKB), a poorly characterized member of the tRNA-modifying EKC/KEOPS complex, as the most significant vulnerability in TP53-mutated cancer cell lines. In vitro and in vivo, across multiple benign-immortalized and cancer cell lines, we confirmed that TPRKB knockdown in TP53-deficient cells significantly inhibited proliferation, with minimal effect in TP53 wild-type cells. TP53 reintroduction into TP53-null cells resulted in loss of TPRKB sensitivity, confirming the importance of TP53 status in this context. In addition, cell lines with mutant TP53 or amplified MDM2 (E3-ubiquitin ligase for TP53) also showed high sensitivity to TPRKB knockdown, consistent with TPRKB dependence in a wide array of TP53-altered cancers. Depletion of other EKC/KEOPS complex members exhibited TP53-independent effects, supporting complex-independent functions of TPRKB. Finally, we found that TP53 indirectly mediates TPRKB degradation, which was rescued by coexpression of PRPK, an interacting member of the EKC/KEOPS complex, or proteasome inhibition. Together, these results identify a unique and specific requirement of TPRKB in a variety of TP53-deficient cancers.

Implications:
Cancer cells with genomic alterations in TP53 are dependent on TPRKB.
Egyptian Cultural Expansionism: Taha Hussein Confronts the French in North Africa (1950-1952)
Authors: Ahmed Hussam R. 
Published: May 2019

AbstractThis article examines Taha Hussein’s (1889-1973) efforts as minister of public instruction to create Egyptian cultural institutes in Europe and North Africa between 1950 and 1952. While scholars have explored the Egyptian interest in the Mashriq before 1952, the details of Hussein’s hitherto unknown conflict with the French authorities over the creation of such institutes in the Maghrib show that Egypt also sought to officially extend its influence to the Maghrib before Nasser came to power. The article explores how Egypt and France articulated their cultural policies in the region as Egypt tried to assert itself as the guardian of Arabic and Islamic studies. Moreover, the article shows that despite Hussein’s ties to France and his controversial claim that culture should transcend politics, his negotiations reveal that the promotion of culture was his political strategy to assert an Egyptian influence, and push back against French colonial policies in North Africa.
Geostationary Satellite over East Africa Observed from Kitt Peak, Arizona
Authors: Livingston William 
Published: May 2019

AbstractGeo-stats are geostationary communication satellites in nearly circular orbits, in the equatorial plane of the Earth, and with an orbital period of one sidereal day. If these three conditions are met, an artificial satellite will be stationary above the Earth. They are usually invisible to the unaided eye (limit of magnitude 6), since the geo-stat’s average brightness is magnitude 12. At night, stars will trail through a fixed camera time exposure of this scene. We have learned how to photograph them using a fixed simple camera from Kitt Peak Mountain in Arizona. We give examples from 30 years of annual observations with identifications from the European Space Agency. One example is over East Africa—yes, seen from Arizona.
Antarctic Verification of the Australian Numerical Weather Prediction Model
Authors: Schroeter Benjamin J. E. , Reid Phil , Bindoff Nathaniel L. , Michael Kelvin 
Published: May 2019

Abstract
The Australian Community Climate and Earth-System Simulator-Global (ACCESS-G) features an atmosphere-only numerical weather prediction (NWP) suite used operationally by the Australian Bureau of Meteorology to forecast weather conditions for the Antarctic. The current operational version of the forecast model, the Australian Parallel Suite v2 (APS2), has been used operationally since early 2016. To date, the performance of the model has been largely unverified for the Antarctic and anecdotal reports suggest challenges for model performance in the region. This study investigates the performance of ACCESS-G south of 50°S over 2017 and finds that model performance degrades toward the poles and in proportion to forecast horizon against a range of performance metrics. The model exhibits persistent negative surface and mean sea level pressure biases around the Adelie Land coast, which is linked to the underrepresentation of model winds to the west, and driven by positive screen temperature biases that inhibit modeled katabatic outflow. These results suggest that an improved representation of boundary layer parameterization could be implemented to improve model performance in the region.
The Impacts of Using Mixed Physics in the Community Leveraged Unified Ensemble
Authors: Gallus William A. , Wolff Jamie , Gotway John Halley , Harrold Michelle , Blank Lindsay , Beck Jeff 
Published: May 2019

Abstract
A well-known problem in high-resolution ensembles has been a lack of sufficient spread among members. Modelers often have used mixed physics to increase spread, but this can introduce problems including computational expense, clustering of members, and members that are not all equally skillful. Thus, a detailed examination of the impacts of using mixed physics is important. The present study uses two years of Community Leveraged Unified Ensemble (CLUE) output to isolate the impact of mixed physics in 36-h forecasts made using a convection-permitting ensemble with 3-km horizontal grid spacing. One 10-member subset of the CLUE used only perturbed initial conditions (ICs) and lateral boundary conditions (LBCs) while another 10-member ensemble used the same mixed ICs and LBCs but also introduced mixed physics. The cases examined occurred during NOAA’s Hazardous Weather Testbed Spring Forecast Experiments in 2016 and 2017. Traditional gridpoint metrics applied to each member and the ensemble as a whole, along with object-based verification statistics for all members, were computed for composite reflectivity and 1- and 3-h accumulated precipitation using the Model Evaluation Tools (MET) software package. It is found that the mixed physics increases variability substantially among the ensemble members, more so for reflectivity than precipitation, such that the envelope of members is more likely to encompass the observations. However, the increased variability is mostly due to the introduction of both substantial high biases in members using one microphysical scheme, and low biases in other schemes. Overall ensemble skill is not substantially different from the ensemble using a single physics package.
Methodological Approaches and Recommendations for Functional Near-Infrared Spectroscopy Applications in HF/E Research
Authors: Zhu Yibo , Rodriguez-Paras Carolina , Rhee Joohyun , Mehta Ranjana K. 
Published: May 2019

Objective The objective of this study was to systematically document current methods and protocols employed when using functional near-infrared spectroscopy (fNIRS) techniques in human factors and ergonomics (HF/E) research and generate recommendations for conducting and reporting fNIRS findings in HF/E applications. Method A total of 1,687 articles were identified through Ovid-MEDLINE, PubMed, Web of Science, and Scopus databases, of which 37 articles were included in the review based on review inclusion/exclusion criteria. Results A majority of the HF/E fNIRS investigations were found in transportation, both ground and aviation, and in assessing cognitive (e.g., workload, working memory) over physical constructs. There were large variations pertaining to data cleaning, processing, and analysis approaches across the studies that warrant standardization of methodological approaches. The review identified major challenges in transparency and reporting of important fNIRS data collection and analyses specifications that diminishes study replicability, introduces potential biases, and increases likelihood of inaccurate results. As such, results reported in existing fNIRS studies need to be cautiously approached. Conclusion To improve the quality of fNIRS investigations and/or to facilitate its adoption and integration in different HF/E applications, such as occupational ergonomics and rehabilitation, recommendations for fNIRS data collection, processing, analysis, and reporting are provided.
Efficacy of galcanezumab in patients with chronic migraine and a history of preventive treatment failure
Authors: Ruff Dustin D , Ford Janet H , Tockhorn-Heidenreich Antje , Sexson Matthew , Govindan Sriram , Pearlman Eric M , Wang Shuu-Jiun , Khan Arif , Aurora Sheena K 
Published: May 2019

BackgroundEfficacy of galcanezumab in chronic migraine has been demonstrated in a pivotal Phase 3 study. Here, we assess efficacy in patients who have failed ≥2 and ≥1 prior migraine preventives for efficacy and/or safety reasons, and in those who never failed.Study design/methodsREGAIN (NCT02614261) was a Phase 3, randomized, double-blind, placebo-controlled study in patients with chronic migraine. Patients were randomized 2:1:1 to receive placebo, galcanezumab 120 mg/240 mg once monthly during a double-blind treatment period lasting three months. Subgroup analyses were conducted among patients who failed ≥2 and ≥1 prior preventives and who never failed previously. Outcomes assessed were change from baseline in number of monthly migraine headache days, proportion of patients with ≥50% and ≥75% response (reduction in monthly migraine headache days), change in number of monthly migraine headache days with acute medication use and change in patient functioning per Migraine-Specific Quality of Life Questionnaire Role Function Restrictive (MSQ RF-R) domain score.ResultsTreatment with galcanezumab versus placebo resulted in significant improvements ( p < 0.01) in overall reduction (Months 1–3) from baseline in the number of monthly migraine headache days in patients with prior failures (LS mean change [SE]: ≥2 prior failures: galcanezumab 120 mg: −5.35 (0.71); galcanezumab 240 mg: −2.77 (0.66); placebo: −1.01 (0.54); ≥1 prior failures: galcanezumab 120 mg: −5.53 (0.60), galcanezumab 240 mg: −3.53 (0.59); placebo: −2.02 (0.49). Similarly, significant results were seen with galcanezumab versus placebo for ≥50% and ≥75% response rates, reductions in acute medication use and improvements in MSQ RF-R domain score. In the subgroup with no prior preventive failures, results were statistically significant for the 240 mg galcanezumab group versus placebo on all outcome measures, and for the 120 mg group on the reduction in migraine headache days with acute medication use. There was also a higher placebo response observed in the patients with no prior preventive failures.ConclusionGalcanezumab is consistently efficacious versus placebo in reducing monthly migraine headache days and several other key outcomes in patients with chronic migraine who have failed ≥2 or ≥1 preventives previously. In the subgroup with no prior failures, greater numerical differences were seen with galcanezumab, but statistical separation from placebo varied by dose and outcome.Clinicaltrials.gov identifier numberNCT02614261.
Comparing migraine with and without aura to healthy controls using RNA sequencing
Authors: Kogelman Lisette JA , Falkenberg Katrine , Halldorsson Gisli H , Poulsen Lau U , Worm Jacob , Ingason Andres , Stefansson Hreinn , Stefansson Kari , Hansen Thomas F , Olesen Jes 
Published: May 2019

Background Migraine mechanisms are *These authors contributed equally to this work. only partly known. Some studies have previously described genes differentially expressed between blood from migraineurs and controls. The objective of this study was to describe gene expression in subtypes of migraine outside of attack and in healthy controls. Methods We extensively phenotyped 17 migraine without aura and nine migraine with aura female patients, and 20 age-matched female controls. Cubital venous blood was RNA sequenced. Genes differentially expressed between migraineurs (migraine without aura and migraine with aura) and controls, and between migraine without aura and migraine with aura were identified using a case-control design. A co-expression network was constructed to investigate the difference between migraineurs and healthy controls at the network level. Results We found two differentially expressed genes: NMNAT2 and RETN. Both were differentially expressed between migraine with aura and controls, but they could not be replicated in an independent cohort. Co-expression network analysis resulted in one cluster of highly interconnected genes that was nominally significantly associated with migraine; however, no pathways or gene ontology terms were detected. Conclusions We showed no clear distinct difference in gene expression profiles of peripheral blood of migraineurs and controls and were not able to replicate findings from previous studies. A larger sample size may be needed to detect minor differences.