bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer
Authors: Wardley Andrew , Cortes Javier , Provencher Louise , Miller Kathy , Chien A. Jo , Rugo Hope S. , Steinberg Joyce , Sugg Jennifer , Tudor Iulia C. , Huizing Manon , Young Robyn , Abramson Vandana , Bose Ron , Hart Lowell , Chan Stephen , Cameron David , Wright Gail S. , Graas Marie-Pascale , Neven Patrick , Rocca Andrea , Russo Stefania , Krop Ian E. 
Published: February 2021

Abstract
Purpose
Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab.

Methods
Eligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status ≤ 1, no history of brain metastases, and previously received ≥ 1 anti-HER2 regimen for advanced disease. Patients received 160 mg oral enzalutamide daily and 6 mg/kg intravenous trastuzumab every 21 days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24 weeks (CBR24); secondary end points included progression-free survival (PFS) and safety.

Results
Overall, 103 women were enrolled [median age 60 years (range 34–83)]; 62% had received ≥ 3 lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24 weeks (19%), was 24% in the efficacy evaluable set (n = 89). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4 months (95% confidence interval 2.0–3.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade ≥ 3 reported in ≥ 3 patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs.

Conclusions
Enzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination.

ClinicalTrials.gov number
NCT02091960
Online measurement of floc size, viscosity, and consistency of cellulose microfibril suspensions with optical coherence tomography
Authors: Lauri Janne , Haavisto Sanna , Salmela Juha , Miettinen Arttu , Fabritius Tapio , Koponen Antti I. 
Published: February 2021

AbstractIn this study, cellulose microfibril (CMF) suspensions were imaged during pipe flow at consistencies of 0.4%, 1.0%, and 1.6% with optical coherence tomography (OCT) to obtain images of the structure and the local velocity of the suspension. The viscosities obtained by combining pressure loss measurement with the OCT velocity data showed typical shear thinning behavior and were in excellent agreement with viscosities obtained with ultrasound velocity profiling. The structural OCT images were used to calculate the radial and the axial floc sizes of the suspension. A fit of power law to the geometrical floc size–shear stress data gave the same power law index for all consistencies, suggesting that floc rupture dynamics is independent of consistency. The dependence of viscosity and floc size on shear stress was similar, indicating that the shear thinning behavior of CMF suspensions is closely related to the rupture dynamics of flocs. The results also showed that an apparent attenuation coefficient of the OCT signal can be used to determine the consistency of CMF suspensions.
EphA4 Obstructs Spinal Cord Neuron Regeneration by Promoting Excessive Activation of Astrocytes
Authors: Chen Xiaogang , Zhang Lin , Hua Fu , Zhuang Yu , Liu Huan , Wang Shouguo 
Published: February 2021

AbstractStudies have found that molecular targets that regulate tissue development are also involved in regulating tissue regeneration. Erythropoietin-producing hepatocyte A4 (EphA4) not only plays a guiding role in neurite outgrowth during the development of the central nervous system (CNS) but also induces injured axon retraction and inhibits axon regeneration after spinal cord injury (SCI). EphA4 targets several ephrin ligands (including ephrin-A and ephrin-B) and is involved in cortical cell migration, axon guidance, synapse formation and astrocyte function. However, how EphA4 affects axon regeneration after SCI remains unclear. This study focuses on the effect and mechanism of EphA4-regulated astrocyte function in neuronal regeneration after SCI. Our research found that EphA4 expression increased significantly after SCI and peaked at 3 days post-injury; accordingly, we identified the cellular localization of EphA4 and ephrin-B ligands in neurons and astrocytes after SCI. EphA4 was mainly expressed on the surface of neurons, ephrin-B1 and ephrin-B3 were mainly localized on astrocytes, and ephrin-B2 was distributed on both neurons and astrocytes. To further elucidate the effect of EphA4 on astrocyte function after SCI, we detected the related cytokines secreted by astrocytes in vivo. We found that the levels of neurotrophic factors including nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) increased significantly after SCI (NGF peaked at 3 days and bFGF peaked at 7 days); the expression of laminin and fibronectin increased gradually after SCI; the expression of inflammatory factors [interleukin (IL)-1β and IL-6] increased significantly from 4 h to 7 days after SCI; and the levels of glial fibrillary acidic protein (GFAP), a marker of astrocyte activation, and chondroitin sulphate proteoglycan (CSPG), the main component of glial scars, both peaked at 7 days after SCI. Using a damaged astrocyte model in vitro, we similarly found that the levels of related cytokines increased after injury. Consequently, we observed the effect of damaged astrocytes on neurite outgrowth and regeneration, and the results showed that damaged astrocytes hindered neurite outgrowth and regeneration; however, the inhibitory effect of injured astrocytes on neurite regeneration was reduced following ephrin-B receptor knockdown or inflammatory inhibition at 24 h after astrocyte injury. Our results showed that EphA4 regulates the secretion of neurotrophic factors, adhesion molecules, inflammatory factors and glial scar formation by binding with the ligand ephrin-B located on the surface of astrocytes. EphA4 affects neurite outgrowth and regeneration after SCI by regulating astrocyte function.
An Intricate Quantum Statistical Effect and the Foundation of Quantum Mechanics
Authors: Bopp Fritz W. 
Published: February 2021

AbstractAn intricate quantum statistical effect guides us to a deterministic, non-causal quantum universe with a given fixed initial and final state density matrix. A concept is developed on how and where something like macroscopic physics can emerge. However, the concept does not allow philosophically crucial free will decisions. The quantum world and its conjugate evolve independently, and one can replace fixed final states on each side just with a common matching one. This change allows for external manipulations done in the quantum world and its conjugate, which do not otherwise alter the basic quantum dynamics. In a big bang/big crunch universe, the expanding part can be attributed to the quantum world and the contracting one to the conjugate one. The obtained bi-linear picture has several noteworthy consequences.
Human Activity and Forest Degradation Threaten Populations of the Nigeria–Cameroon Chimpanzee (Pan troglodytes ellioti) in Western Cameroon
Authors: Fotang Chefor , Bröring Udo , Roos Christian , Enoguanbhor Evidence Chinedu , Abwe Ekwoge E. , Dutton Paul , Schierack Peter , Angwafo Tsi Evaristus , Birkhofer Klaus 
Published: February 2021

AbstractIncreased human activities such as commodity-led deforestation, extension of agriculture, urbanization, and wildfires are major drivers of forest loss worldwide. In Cameroon, these activities cause a loss of suitable primate habitat and could ultimately threaten the survival of chimpanzees (Pan troglodytes). We derived independent estimates of the population size of the Endangered Nigeria–Cameroon chimpanzee (Pan troglodytes ellioti) in Kom-Wum Forest Reserve, Cameroon, and surrounding unprotected forest areas through 1) direct observations, 2) camera trapping, 3) distance sampling, 4) marked nest counts, and 5) standing crop nest counts. In addition, we georeferenced signs of chimpanzee and human activity along line transects. We used a generalized linear mixed model to predict the occurrence of chimpanzees in response to edge length (measured as the perimeter of core forest patches), core area of forest patches (measured as area of forest patches beyond an edge width of 100 m), habitat perforation (measured as the perimeter of nonforested landscape within core forest patches), patch size(measured as area of forest patches), and forest cover. Chimpanzee density estimates ranged from 0.1 (direct observation) to 0.9 (distance sampling) individuals km−2depending on estimation method with a mean nest group size of 7 ± 5.4 (SD). The mean encounter rate for signs of chimpanzee activity was significantly higher in mature forests (2.3 signs km−1) than in secondary forests (0.3 signs km−1) and above 1000 m elevation (4.0 signs km−1) than below 1000 m (1.0 signs km−1). The mean encounter rate for signs of human activity was significantly higher in secondary (8.0 signs km−1) than in mature forests (0.9 signs km−1). Secondary forests, habitat perforation, and edge length had a significant negative effect on the occurrence of chimpanzee signs. Overall, human activity and forest degradation affected the number of observed chimpanzee signs negatively. Regular antipoaching patrols and reforestation programs in degraded areas could potentially reduce threats to populations of endangered species and may increase suitable habitat area.
Variation in the fatty acid profiles of two cold water diatoms grown under different temperature, light, and nutrient regimes
Authors: Spilling Kristian , Seppälä Jukka , Schwenk Dagmar , Rischer Heiko , Tamminen Timo 
Published: February 2021

AbstractThere is a growing demand for marine omega-3 fatty acids (FAs) that is produced in high amounts by some microalgae. Here we determined the FA profiles of two cold water adapted diatoms,Chaetoceros wighamiiandThalassiosira baltica. The cultures were acclimated to different temperatures (3, 7, 11, 15, and 19 °C) and irradiance (20, 40, 130, and 450 μmol photons m−2s−1) and the FA profiles were determined in exponential and stationary growth phases, the latter induced by different nutrient limitation (N, P, and Si). The maximum growth rate was obtained by both species at 11 °C, ≥ 130 μmol photons m−2s−1and was 0.8 day−1and 0.6 day−1forC. wighamiiandT. baltica, respectively. Both species contained relatively high amounts of eicosapentaenoic acid (EPA).Thalassiosira balticaaccumulated maximally ~ 30 mg EPA g−1ash-free dry weight (AFDW) under Si-limitation. The content of docosahexaenoic acid (DHA) was lower, reaching up to 4 mg DHA g−1AFDW inT. baltica. The concentration of EPA correlated positively with the chlorophylla:carbon ratio, suggesting that it is bound to membranes in the photosynthetic apparatus and the EPA content inT. balticawas high enough to consider it as a potent candidate for cultivation under cold (< 15 °C) conditions. Covering a wide range of environmental conditions, the strongest differentiation in FA profiles was observed between the species with the growth phase/nutrient limitation pattern as the second most important driver of the FA composition.
Atmospheric pressure metal organic chemical vapor deposition of thin germanium films
Authors: Fritzsche Ronny , Zahn Dietrich R. , Mehring Michael 
Published: February 2021

AbstractThe deposition of thin germanium films by atmospheric pressure metal organic chemical vapor deposition at temperatures below 400 °C on substrates such as silicon wafers, float glass, and polyimide (Kapton®) using the diorganogermanes GeH2Cp4M2 and GeH2Cp*2 as molecular precursors is described. The deposition rates and thus the layer thicknesses can be varied by temperature and time to give layers with a thickness in the nanometer range. The homogeneity and roughness of the deposited films were analyzed by means of atomic force microscopy measurements showing the formation of smooth and uniform surfaces with roughnesses of the films in the range of (1 ± 0.15) nm to (4.5 ± 1.5) nm. Films with thicknesses between 50 and 750 nm were deposited and analyzed by Raman spectroscopy, vis–NIR spectroscopy, electron microscopy, energy dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). The as-deposited films are composed of amorphous germanium containing approximately 10% of carbon. Using Kapton® as a substrate highly flexible films were obtained.
The small world of German CEOs: a multi-method analysis of the affiliation network structure
Authors: Semenova Elena 
Published: February 2021

AbstractThis paper seeks to understand the structure of corporate networks in the period following the dissolution of Deutschland AG (“Germany Inc.”). For this purpose, affiliation networks among chief executive officers (CEOs) that are based on common membership in various societal organizations will be examined. I apply an innovative mix of methods for studying a sample of CEOs from the 100 top companies in Germany in the 2010s. Based on social network analysis, I show that the overall affiliation network has all features of a small-world network, i.e., a high clustering coefficient and a short path length among the CEOs. The average degree of separation among German CEOs is only two steps. Another innovative contribution of this paper is its study of the linkage between affiliation network features and patterns of corporate recruitment. Using multiple correspondence analysis, I show that different subgroups of the overall affiliation network have their specific network characteristics and recruitment patterns. Within the network, managers from automotive and technical engineering often assume brokerage positions, while managers from the trade branch are largely isolated. This study shows that the affiliation networks and corporate recruitment patterns are interlinked; the transformation of corporate networks is a dynamic outcome of interrelations among different subgroups within the network, each with distinct educational, professional, and network characteristics.
Catalytic antibodies in the bone marrow and other organs of Th mice during spontaneous development of experimental autoimmune encephalomyelitis associated with cell differentiation
Authors: Aulova Kseniya S. , Urusov Andrey E. , Toporkova Ludmila B. , Sedykh Sergey E. , Shevchenko Yuliya A. , Tereshchenko Valery P. , Sennikov Sergei V. , Budde Thomas , Meuth Sven G. , Orlovskaya Irina A. , Nevinsky Georgy A. 
Published: February 2021

AbstractExact mechanisms of autoimmune disease development are still yet unknown. However, it is known that the development of autoimmune diseases is associated with defects in the immune system, namely, the violation of the bone marrow hematopoietic stem cells (HSCs) differentiation profiles. Different characteristics of autoimmune reaction development in experimental autoimmune encephalomyelitis (EAE) prone Th mice characterizing T-lymphocytes response were analyzed using standard approaches. Profiles of several HSCs differentiation of bone marrow (BFU-E, CFU-E, CFU-GM, CFU-GEMM, T- and B-lymphocytes) of Th male and female mice during spontaneous development of EAE were noticeably different. Patterns of total lymphocytes, B- and T-cells proliferation in several different organs (bone marrow, blood, spleen, thymus, and lymph nodes) were also remarkably different. In addition, there were in time noticeable differences in their changes for some organs of male and female mice. Characters of changes in the profiles of CD4 and CD8 cells proliferation in some organs not always coincide with those for total T lymphocytes. The changes in the differentiation profiles of HSCs and the level of lymphocytes proliferation in the bone marrow and other organs were associated with the increase in the concentration of antibodies against DNA, myelin basic protein, and myelin oligodendrocyte glycoprotein, and catalytic antibodies hydrolyzing these substrates. Despite some differences in changes in the analyzed parameters, in general, the spontaneous development of EAE in male and female mice occurs to some extent in a comparable way.
Optimal Operation of Transient Gas Transport Networks
Authors: Hoppmann-Baum Kai , Hennings Felix , Lenz Ralf , Gotzes Uwe , Heinecke Nina , Spreckelsen Klaus , Koch Thorsten 
Published: February 2021

AbstractIn this paper, we describe an algorithmic framework for the optimal operation of transient gas transport networks consisting of a hierarchical MILP formulation together with a sequential linear programming inspired post-processing routine. Its implementation is part of the KOMPASS decision support system, which is currently used in an industrial setting. Real-world gas transport networks are controlled by operating complex pipeline intersection areas, which comprise multiple compressor units, regulators, and valves. In the following, we introduce the concept of network stations to model them. Thereby, we represent the technical capabilities of a station by hand-tailored artificial arcs and add them to network. Furthermore, we choose from a predefined set of flow directions for each network station and time step, which determines where the gas enters and leaves the station. Additionally, we have to select a supported simple state, which consists of two subsets of artificial arcs: Arcs that must and arcs that cannot be used. The goal is to determine a stable control of the network satisfying all supplies and demands. The pipeline intersections, that are represented by the network stations, were initially built centuries ago. Subsequently, due to updates, changes, and extensions, they evolved into highly complex and involved topologies. To extract their basic properties and to model them using computer-readable and optimizable descriptions took several years of effort. To support the dispatchers in controlling the network, we need to compute a continuously updated list of recommended measures. Our motivation for the model presented here is to make fast decisions on important transient global control parameters, i.e., how to route the flow and where to compress the gas. Detailed continuous and discrete technical control measures realizing them, which take all hardware details into account, are determined in a subsequent step. In this paper, we present computational results from the KOMPASS project using detailed real-world data.
Liability, culpability, and luck
Authors: Nelkin Dana Kay 
Published: February 2021

AbstractThis paper focuses on the role of culpability in determining the degree of liability to defensive harm, and asks whether there are any restrictions on when culpability is relevant to liability. A natural first suggestion is that it is only relevant (or at least is significantly enhanced) when combined with an actual threat of harm in the situation in which defensive harm becomes salient as a means of protection. The paper begins by considering the question of whether two people are equally liable to defensive harm in a situation if both culpably intend to harm another, but due to circumstances outside the control of the two people only one has a chance of succeeding in causing harm. I argue that there is no difference in liability between the two. I then turn to a kind of slippery slope challenge that accepting this conclusion would lead to a vast over-inclusiveness in those liable to defensive harm, and consider a recent attempt at meeting it that requires that a person’s culpability can only affect liability if it concerns the very situation in which defensive harm is relevant. Finally, I put forward and assess a new way of meeting the challenge that appeals to a particular conception of culpability together with auxiliary theses concerning how culpability can decrease over time, among others.
Renal complications in patients with chronic hypoparathyroidism on conventional therapy: a systematic literature review
Authors: Gosmanova Elvira O. , Houillier Pascal , Rejnmark Lars , Marelli Claudio , Bilezikian John P. 
Published: February 2021

AbstractA systematic literature review was performed to summarize the frequency and nature of renal complications in patients with chronic hypoparathyroidism managed with conventional therapy. Methodology was consistent with the recommendations outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Peer-reviewed journal articles with specified medical subject heading terms were identified using the PubMed, EMBASE, and Cochrane databases. Data were extracted from eligible articles based on prespecified parameters for clinical outcomes of renal calcifications and disease. Because of the heterogeneity of the data, a meta-analysis could not be conducted. From 1200 potentially relevant articles, data were extracted from 13 manuscripts that reported data for ≥1 of the 19 predefined renal outcomes for ≥10 adult patients (n = 11 manuscripts) or pediatric patients (n = 2 manuscripts). The collective data provide evidence that adult and pediatric patients with chronic hypoparathyroidism and treated with conventional therapy (oral calcium and active vitamin D) had an increased risk of renal complications. The reported rate of nephrolithiasis was up to 36%, with the lowest rates in studies reporting shorter duration of disease. The rate of nephrocalcinosis was up to 38%. Some studies reported a combined nephrolithiasis/nephrocalcinosis outcome of 19% to 31%. Data for renal disease that encompassed a range of renal insufficiency to chronic kidney disease were reported in 10 articles; the reported rates ranged from 2.5% to 41%. In patients who receive long-term treatment with oral calcium and active vitamin D, chronic hypoparathyroidism may be associated with an increased risk of renal complications compared with the general population.