bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation and chemotherapy variable response induced by tumor cell hypoxia: impact of radiation dose, anticancer drug, and type of cancer
Authors: Ibrahim Ayman M. , Nady Soad , Shafaa Medhat W. , Khalil Magdy M. 
Published: April 2022

AbstractHypoxia is a condition in which proliferating tumor cells are deprived of oxygen due to limited blood supply from abnormal tumor microvasculature. This study aimed to investigate the molecular changes that occur in tumor cell hypoxia with special emphasis placed on the efficacy of chemotherapeutic and radiation-related effects. Four commercially available chemotherapeutic agents: cisplatin, cyclophosphamide, doxorubicin, and 5-fluorouracil, were tested for their cytotoxic activity on the cancer cell lines PC3 (prostate), HepG2 (liver), and MCF-7 (breast). Tumor cell lines under hypoxia were treated with both IC50 concentrations of the different chemotherapeutic agents and irradiated with 5 and 10 Gy using a 137Cs gamma source. Hypoxia-inducible factor-1α (HIF-1α) protein levels were examined using an ELISA assay. Hypoxic cells showed a significant change in cell viability to all chemotherapeutic agents in comparison to normoxic controls. HepG2 cells were more resistant to the cytotoxic drug doxorubicin compared to other cancer cell lines. The flow cytometric analysis showed that hypoxic cells have lower levels of total apoptotic cell populations (early and late apoptosis) compared to normoxic cells suggesting decreased hypoxia-induced apoptosis in cancer cells. The highest reduction in HIF-1α level was observed in the MCF-7 cell line (95.5%) in response to the doxorubicin treatment combined with 10 Gy irradiation of cells. Chemoradiotherapy could result in minimal as well as a high reduction of HIF-1α based on cell type, type of chemotherapy, and amount of ionizing radiation. This study highlights future research work to optimize a combined chemoradiotherapeutic regime in individual cancer cell hypoxia.
Early stage breast cancer follow-up in real-world clinical practice: the added value of cell free circulating tumor DNA
Authors: La Rocca E. , De Santis M. C. , Silvestri M. , Ortolan E. , Valenti M. , Folli S. , de Braud F. G. , Bianchi G. V. , Scaperrotta G. P. , Apolone G. , Daidone M. G. , Cappelletti V. , Pruneri G. , Di Cosimo S. 
Published: April 2022

Abstract
Purpose
Physical examinations and annual mammography (minimal follow-up) are as effective as laboratory/imaging tests (intensive follow-up) in detecting breast cancer (BC) recurrence. This statement is now challenged by the availability of new diagnostic tools for asymptomatic cases. Herein, we analyzed current practices and circulating tumor DNA (ctDNA) in monitoring high-risk BC patients treated with curative intent in a comprehensive cancer center.

Patients and methods
Forty-two consecutive triple negative BC patients undergoing neoadjuvant therapy and surgery were prospectively enrolled. Data from plasma samples and surveillance procedures were analyzed to report the diagnostic pattern of relapsed cases, i.e., by symptoms, follow-up procedures and ctDNA.

Results
Besides minimal follow-up, 97% and 79% of patients had at least 1 non-recommended imaging and laboratory tests for surveillance purposes. During a median follow-up of 5.1(IQR, 4.1–5.9) years, 13 events occurred (1 contralateral BC, 1 loco-regional recurrence, 10 metastases, and 1 death). Five recurrent cases were diagnosed by intensive follow-up, 5 by symptoms, and 2 incidentally. ctDNA antedated disseminated disease in all evaluable cases excepted two with bone-only and single liver metastases. The mean time from ctDNA detection to suspicious findings at follow-up imaging was 3.81(SD, 2.68), and to definitive recurrence diagnosis 8(SD, 2.98) months. ctDNA was undetectable in the absence of disease and in two suspected cases not subsequently confirmed.

Conclusions
Some relapses are still symptomatic despite the extensive use of intensive follow-up. ctDNA is a specific test, sensitive enough to detect recurrence before other methods, suitable for clarifying equivocal imaging, and exploitable for salvage therapy in asymptomatic BC survivors.
Voronoi-Based Discrete Element Analyses to Assess the Influence of the Grain Size and Its Uniformity on the Apparent Fracture Toughness of Notched Rock Specimens
Authors: Justo J. , Konietzky H. , Castro J. 
Published: April 2022

AbstractThe fracture toughness reflects the rock resistance to crack propagation, and therefore represents an important parameter for rock fracture assessments. From a strict point of view, the real fracture toughness ($$\it {K}_{\mathrm{\it IC}}$$

K
IC

) corresponds to a cracked situation in which the notch radius is theoretically equal to zero. However, most of the defects in rocks have a finite radius and, therefore, should be studied as notch-type defects. Here, the notch effect is numerically studied together with the influence of the grain size and the sorting coefficient (grain size uniformity) on the apparent fracture toughness ($$\it {K}_{\mathrm{\it IN}}$$

K
IN

). To this end, several four-point bending tests with different U-shaped notch radii, mean grain sizes and degrees of uniformity in grain size and shape have been simulated using the Discrete Element Method. In order to represent the grains of the rocks, the Voronoi tessellation is used to create randomly sized and distributed polygonal blocks. These Voronoi polygons have been defined, on the one hand, by an average edge length of 1, 2 and 3 mm, and, on the other hand, by a different number of iterations ($$n$$
n
) in the relaxation process during the generation of the polygons, which defines the grain size uniformity. The numerical analyses performed and the interpretation of the results show a clear notch effect in all the studied cases, as the apparent fracture toughness ($$\it {K}_{\mathrm{\it IN}}$$

K
IN

) increases with notch radius. Finally, the obtained stress fields at the notch tip have been compared to those obtained from the traditional finite element method.
Botulinum toxin therapy: past, present and future developments
Authors: Dressler Dirk , Johnson Eric A. 
Published: April 2022

AbstractAlthough botulinum toxin (BT) is now being used in a large number of different indications in numerous medical specialties, there is still dynamic and rapid development. Treatment algorithms were improved by the introduction of BT short-interval therapy, BT high-dose therapy and improved dosing guidelines. Ultrasound guidance may be helpful in special situations. New indication areas including depression and inflammatory processes are being explored. Drug development projects are mainly focusing on onabotulinumtoxinA analogues, some are addressing liquid preparations and modifications of BT's duration of action. Recombinant BT may simplify production processes. Cell-based assays for potency measurement will soon be required by registration authorities. Treatment algorithms will be further refined and indications will be expanded. New indication areas are still uncertain. BT type A will remain the drug substance of choice. Removal of complexing proteins seems logical. Whether there is a need for BT drugs with modified duration of action and for liquid preparations, is unclear. Bringing BT therapy to those who need it, is the biggest challenge. Current high-price business models need to be changed, either by employing a biosimilar registration approach or by referring to companies from countries where business models are based on different cost structures.
Simultaneous Determination of Carvedilol, Enalaprilat, and Perindoprilat in Human Plasma Using LC–MS/MS and Its Application to a Pharmacokinetic Pilot Study
Authors: Joubert Andre , Kellermann Tracy , Joubert Anton , van der Merwe Marthinus , Norman Jennifer , Castel Sandra , Sliwa Karen , Maartens Gary , Sinxadi Phumla , Wiesner Lubbe 
Published: April 2022

AbstractA method for the extraction and quantification of carvedilol, enalaprilat, and perindoprilat in 50 µL human plasma, using high-performance liquid chromatography with tandem mass spectrometry (LC–MS/MS) detection was developed and validated. Samples were prepared via protein precipitation with chromatographic separation on a Restek Ultra II Biphenyl column using gradient elution at a corresponding flowrate of 300 µL/min. Electrospray ionisation with mass detection at unit resolution in the multiple reaction monitoring (MRM) mode on an AB Sciex API 5500 mass spectrometer was used. Accuracy, precision, selectivity, sensitivity, matrix effects, recovery, process efficiency, and stability were assessed over the validation period. The assay was validated over the calibration range 0.2–200 ng/mL for all three analytes. The inter- and intra-day precision expressed as the coefficient of variation (CV) and accuracy (%Nom) all fell within acceptable limits. The overall recovery was calculated as 72.9%, 77.1%, and 77.0% for carvedilol, enalaprilat, and perindoprilat respectively, with the recovery being shown to be reproducible at the low, medium and high end of the calibration range for all three analytes. The method proved to be specific for all three analytes with no significant matrix effects observed. The validated method facilitated the analysis of carvedilol, enalaprilat, and perindoprilat in human plasma collected from adults as part of a pilot pharmacokinetic study. This validated analytical method lays the foundation for determining adherence in heart failure patients prescribed with carvedilol, enalapril and perindopril.
Model-based reasoning using answer set programming
Authors: Wotawa Franz , Kaufmann David 
Published: April 2022

AbstractDiagnosis, i.e., the detection and identification of faults, provides the basis for bringing systems back to normal operation in case of a fault. Diagnosis is a very important task of our daily live, assuring safe and reliable behavior of systems. The automation of diagnosis has been a successful research topic for several decades. However, there are limitations due to complexity issues and lack of expressiveness of the underlying reasoning mechanisms. More recently logic reasoning like answer set programming has gained a lot of attention and practical use. In this paper, we tackle the question whether answer set programming can be used for automating diagnosis, focusing on industrial applications. We discuss a formalization of the diagnosis problem based on answer set programming, introduce a general framework for modeling systems, and present experimental results of an answer set programming based diagnosis algorithm. Past limitations like not being able to deal with numerical operations for modeling can be solved to some extent. The experimental results indicate that answer set programming is efficient enough for being used in diagnosis applications, providing that the underlying system is of moderate size. For digital circuits having less than 500 components, diagnosis time has been less than one second even for computing triple fault diagnoses.
Usage of Tyre Derived Aggregates as backfill around buried pipelines crossing strike-slip faults; model tests
Authors: Karaman Mustafa , Demirci Hasan Emre , Ecemis Nurhan , Bhattacharya Subhamoy 
Published: April 2022

AbstractBuried pipelines crossing active faults are exposed to excessive soil forces under fault movements due to large relative movement between pipes and the soil surrounding them. As a result, extreme longitudinal strains develop within pipelines under large fault movements and this leads to pipeline failures. Several seismic mitigation techniques were proposed to improve the performance of buried pipelines crossing active faults. In this study, the potential of using Tyre Derived Aggregates (TDA) as a backfill material for mitigating the effects of strike-slip faulting are investigated through physical model tests. First, the details of the physical model test setup and model configuration are presented. Then a comparative study is carried out to study the effect of TDA content in the backfill and trench configurations on TDA mitigation. Model tests revealed that using a sloped trench with 100% TDA content in the backfill can decrease peak axial pipe strains up to 62% and peak bending strains up to 19%. It is observed that enlarging the trench and using an inclined trench improve the performance of the TDA mitigation technique.
Circulating tumor cell detection: A prospective comparison between CellSearch® and RareCyte® platforms in patients with progressive metastatic breast cancer
Authors: Dirix Luc , Buys Andy , Oeyen Steffy , Peeters Dieter , Liègeois Vincent , Prové Annemie , Rondas Dieter , Vervoort Liesbet , Mariën Véronique , Laere Steven Van , Vermeulen Peter 
Published: April 2022

Abstract
Purpose
Circulating tumor cells (CTCs) are prognostic in patients with breast cancer. Several technical platforms exist for their enumeration and characterization. Comparative studies between these platforms are scarce. The RareCyte CTC detection is theoretically more sensitive than the established CellSearch platform, which identifies only CTCs that express EpCAM and cytokeratin.
This study prospectively compares CTC enumeration in patients with breast cancer in a paired analysis using these two platforms. It investigates survival outcomes in groups defined by a CTC count threshold.

Design
CTC enumeration was performed on 100 samples obtained from 86 patients with progressive metastatic breast cancer (MBC) in two independent laboratories each blinded to the clinical data and the results from the other platform.

Results
One hundred paired samples were collected and CTC counts were determined using the CellSearch and RareCyte CTC platforms. In total, 65% and 75% of samples had at least one detectable CTC in 7.5 mL blood with the CellSearch and the RareCyte systems, respectively. CTC counts with the CellSearch system ranged from 0 to 2289 with a median of 3 CTCs, the RareCyte CTC counts ranged from 0 to 1676 with a median of 3 CTCs. The number of samples with 5 or more CTCs in 7.5 mL of blood (the poor prognosis cut-off validated with the CellSearch system) blood was 45% with the CellSearch test and 48% with the RareCyte test. CTC counts quantified with the CellSearch and the RareCyte systems were strongly correlated (Spearman’s r = 0.8235 (0.7450–0.8795) p < 0.001).
86 patients were included for Kaplan–Meier survival analysis. An increased mortality risk in patients with CellSearch of 5 CTCs or more per 7.5 mL blood, with a log-rank hazard ratio of 5.164 (2.579–10.34) (p < 0.001) was confirmed. The survival analysis with RareCyte CTC counts with the identical cut-off showed a significantly impaired survival with a hazard ratio of 4.213 (2.153–8.244) (p < 0.001).

Conclusion
Our data demonstrate the analytical and prognostic equivalence of CellSearch and RareCyte CTC enumeration platforms in patients with MBC using the CellSearch cut-off. This is the first demonstration of prognostic significance using the RareCyte platform.
Overlong simulations of the solar system dynamics with two alternating step-lengths
Authors: Mikkola Seppo , Lehto Harry J. 
Published: April 2022

AbstractWe compare the performance of four symplectic integration methods with leading order symplectic corrector in simulations of the Solar System. These simulations cover 10 Gyr. They are longer than the astrophysical predicted future of the present-day Solar System, thus this work is mainly a study of the integration methods. For the outer Solar System simulation, where the used stepsize was 100 days, the energy errors do not show any secular evolution. The maximum errors show a dependence on the method. The simulations of the full Solar System from Mercury, and including Pluto as a test particle, were calculated with a stepsize of 7 days. The energy errors behave somewhat differently having a small secular behavior. This may due to the short timestep and the short period of the planet Mercury or some small round off error produced by the code. Comparison of the eccentricity evolution’s within simulations show that some planets are dynamically strongly coupled. Venus and Earth form a dynamical pair, also Jupiter and Saturn form a dynamical pair. The FFT of the analysis of the simulations suggests that all the giant planets form a single dynamical quadruple system. The orbit of Mercury is possibly unstable. Each simulation is stopped when Mercury is expelled. All the methods show similar results for times less than $$30\, $$

30

Myr in the way that the results for orbital elements are same within plotting precision. Inclusion of Mercury in simulations shortens the Solar System e-folding time to $$3.3\, $$

3.3

Myr. It is clear that chaos has a strong effect in the evolution of orbital elements, especially eccentricities. This is easily seen in Mercury’s orbit when the simulation time exceeds at least $$30\, $$

30

Myr. Our low-order simulations seem to match high-order methods over long timescales.
Second order semi-smooth Proximal Newton methods in Hilbert spaces
Authors: Pötzl Bastian , Schiela Anton , Jaap Patrick 
Published: April 2022

AbstractWe develop a globalized Proximal Newton method for composite and possibly non-convex minimization problems in Hilbert spaces. Additionally, we impose less restrictive assumptions on the composite objective functional considering differentiability and convexity than in existing theory. As far as differentiability of the smooth part of the objective function is concerned, we introduce the notion of second order semi-smoothness and discuss why it constitutes an adequate framework for our Proximal Newton method. However, both global convergence as well as local acceleration still pertain to hold in our scenario. Eventually, the convergence properties of our algorithm are displayed by solving a toy model problem in function space.
On the evolution and impact of architectural smells—an industrial case study
Authors: Sas Darius , Avgeriou Paris , Uyumaz Umut 
Published: April 2022

AbstractArchitectural smells (AS) are notorious for their long-term impact on the Maintainability and Evolvability of software systems. The majority of research work has investigated this topic by mining software repositories of open source Java systems, making it hard to generalise and apply them to an industrial context and other programming languages. To address this research gap, we conducted an embedded multiple-case case study, in collaboration with a large industry partner, to study how AS evolve in industrial embedded systems. We detect and track AS in 9 C/C++ projects with over 30 releases for each project that span over two years of development, with over 20 millions lines of code in the last release only. In addition to these quantitative results, we also interview 12 among the developers and architects working on these projects, collecting over six hours of qualitative data about the usefulness of AS analysis and the issues they experienced while maintaining and evolving artefacts affected by AS. Our quantitative findings show how individual smell instances evolve over time, how long they typically survive within the system, how they overlap with instances of other smell types, and finally what the introduction order of smell types is when they overlap. Our qualitative findings, instead, provide insights on the effects of AS on the long-term maintainability and evolvability of the system, supported by several excerpts from our interviews. Practitioners also mention what parts of the AS analysis actually provide actionable insights that they can use to plan refactoring activities.
Thermodynamics of Melting in Colloids and Helium
Authors: Brady Robert M. , Samulski Edward T. 
Published: April 2022

AbstractEnhanced fluctuations pervade a phase near a transition point. This phenomenon was observed in recent simulations of polyhedral particles, where rod-shaped vacancy defects diffused through a solid phase carrying mass flow. The defects proliferated at the melting point, magnifying the mass flow to liquid proportions. Here, we show that the number of vacancies increases on heating or lowering the pressure, in accordance with Boltzmann statistics, but the Boltzmann equilibrium becomes unstable at a threshold number resulting in the first-order melting transition. The instability is driven by an increase in entropy if the defects repel, or by a reduction in enthalpy if they attract. A corresponding thermodynamic instability occurs in other melting transitions, including in argon, colloids, cryogenic helium and simulations of hard spheres. The statistics of the vacancies explains a long-standing anomaly in the heat capacity of solid helium-4, as well as recent measurements of thermally activated mass flow through solid helium-3. In liquid helium-4, the vacancies conform to Feynman’s atomistic and quantum descriptions of rotons and quantitatively account for associated neutron scattering measurements. Colloids, silicon and sodium also melt ‘re-entrantly’ on elevating the pressure, and we identify quantitative evidence that this transition involves the proliferation of interstitial defects.
Persistence and stability of a class of kinetic compartmental models
Authors: Szederkényi Gábor , Ács Bernadett , Lipták György , Vághy Mihály A. 
Published: April 2022

AbstractIn this paper we show that the dynamics of a class of kinetic compartmental models with bounded capacities, monotone reaction rates and a strongly connected interconnection structure is persistent. The result is based on the chemical reaction network (CRN) and the corresponding Petri net representation of the system. For the persistence analysis, it is shown that all siphons in the Petri net of the studied model class can be characterized efficiently. Additionally, the existence and stability of equilibria are also analyzed building on the persistence and the theory of general compartmental systems. The obtained results can be applied in the analysis of general kinetic models based on the simple exclusion principle.
Fluid dynamic shape optimization using self-adapting nonlinear extension operators with multigrid preconditioners
Authors: Pinzon Jose , Siebenborn Martin 
Published: April 2022

AbstractIn this article we propose a scalable shape optimization algorithm which is tailored for large scale problems and geometries represented by hierarchically refined meshes. Weak scalability and grid independent convergence is achieved via a combination of multigrid schemes for the simulation of the PDEs and quasi Newton methods on the optimization side. For this purpose a self-adapting, nonlinear extension operator is proposed within the framework of the method of mappings. This operator is demonstrated to identify critical regions in the reference configuration where geometric singularities have to arise or vanish. Thereby the set of admissible transformations is adapted to the underlying shape optimization situation. The performance of the proposed method is demonstrated for the example of drag minimization of an obstacle within a stationary, incompressible Navier–Stokes flow.