bluuebunny/crossref_metadata_2025_split huggingface dataset:
The exchange of self-incriminating information of athletes between sports organisations and law enforcement
Authors: Hessert Björn 
Published: July 2021

AbstractSports organisations generally have the burden of proving sports rule violations of sportspersons subject to their rules and regulations. Sports rule violations can generally be proven by any reliable means. A common approach taken by sports organisations in this respect is the implementation of so-called cooperation and reporting obligations embedded in their regulations. On this basis, athletes can be obliged to provide all kind of documentary evidence related or unrelated to the matter under investigation. This may cause problems to the privilege against self-incrimination of athletes. In addition, obtaining self-incriminating information in internal sports investigations carried out by private sports organisations can have legal and personal consequences that go well beyond the professional life of athletes. The integrity of sport has been characterised as a public interest due to the social impact of amateur and professional sports in most societies. As a consequence, negative sports-related conduct, such as doping or the manipulation of sports competitions, has been criminalised in various national laws to protect sporting values and preserve the role model function of athletes for young members of our society. This development has led to cooperation between sports organisations and law enforcement agencies, such as prosecutors and the police. Specifically, both collaborate in order to assist the other party’s investigations of sports rule violations and criminal offences, respectively. However, the exchange of intelligence between sports organisations and law enforcement may cause some legal tension. If the same misconduct of athletes leads to both internal sports investigations and criminal proceedings, athletes could be forced to provide self-incriminating information in internal sports organisations, which could then be subsequently transmitted to law enforcement. This system of intelligence gathering raises serious concerns regarding the procedural fairness thereof, keeping in mind the detrimental effects for sportspersons under investigations. A closer look is thus necessary to the legitimacy of the exchange of intelligence. Therefore, the aim of this article is to shed some light on this issue and clarify if and under what conditions internally obtained evidence can be passed on to law enforcement agencies.
Has the EU Incentive for Drug Repositioning Been Effective? An Empirical Analysis of the “+1” Regulatory Exclusivity
Authors: Liddicoat Johnathon , Liddell Kathleen , Aboy Mateo , Wested Jakob 
Published: July 2021

AbstractEU law incentivises drug marketing authorisation holders (MAHs) to find new uses for their compounds (research known as “repositioning”) by offering them an extra year of market protection if the new use is authorised. This extra year, known as the “+1”, was enacted on limited evidence, and no study has examined its effect since it began. Yet, several leading commentators suggest lengthening the +1. This study assesses the effectiveness of the +1 by analysing all the relevant instances of MAHs repositioning their drugs before and after the +1 came into effect. The results show that: (i) 42.2% of MAHs repositioned their drugs before the +1 came into effect, and (ii) once the +1 did come into effect, it did not increase the percentage of MAHs that repositioned their drugs. This study finds that the +1 failed to increase repositioning and then proceeds to consider reform options, including repealing the law. In doing so, this study takes the first steps towards an evidence-based policy for the topic.
Thyroid autoimmunity and hypothyroidism are associated with deep molecular response in patients with chronic myeloid leukemia on tyrosine kinase inhibitors
Authors: Rodia R. , Pani F. , Caocci G. , La Nasa G. , Simula M. P. , Mulas O. , Velluzzi F. , Loviselli A. , Mariotti S. , Boi F. 
Published: July 2021

Abstract
Purpose
Thyroid alterations including de novo appearance of thyroid autoimmunity are adverse effects of tyrosine kinase inhibitors, used in solid and hematologic cancer therapy, but the relationship between thyroid alterations during this treatment and the outcome of chronic myeloid leukemia remains unclear. Aim of this study was to investigate whether the presence of thyroid alterations may affect the clinical outcome of chronic myeloid leukemia on tyrosine kinase inhibitors.

Methods
We evaluated thyroid function and autoimmunity in 69 chronic myeloid leukemia patients on long-term therapy looking at the association between thyroid abnormalities and disease molecular response.

Results
Overall, 24 of 69 (34.8%) had one or more thyroid abnormalities during therapy. A high percentage of patients (21/69, 30.4%) showed thyroid autoimmunity (positive thyroid autoantibodies with ultrasound hypoechogenicity), while clinical and subclinical hypothyroidism and subclinical hyperthyroidism were, respectively, found in 4 of 69 (5.8%) and 3 of 69 (4.3%) of cases. Second-generation tyrosine kinase inhibitors resulted significantly associated (14/32, 43.7%) with Hashimoto’s thyroiditis, compared to first generation (7/37, 18.9%; p = 0.03). Interestingly, we also found a significant association between euthyroid (14/26, 53.8%) and hypothyroid Hashimoto’s thyroiditis (4/26, 15.4%) in patients with deep molecular response, as compared to euthyroid (3/43, 7%; p = 0.0001) and hypothyroid (0/43, 0%; p = 0.02) Hashimoto’s thyroiditis patients with major molecular response.

Conclusions
Our study confirms and extends our knowledge on the tyrosine kinase inhibitors effects on thyroid, showing that thyroid autoimmunity is frequently observed in chronic myeloid leukemia patients on long-term therapy and is associated with a better oncological response.
Die Vermittlung der Ungleichheit: Zur symbolischen Ordnung sozialer Unterschiede und wohlfahrtsstaatlicher Rationalität in narrativen Konstruktionen der Mittelschicht
Authors: Barbehön Marlon 
Published: July 2021

ZusammenfassungDie Frage, wann eine Gesellschaft soziale Differenzen als Ungleichheiten erfährt und zum Gegenstand öffentlicher Kontroversen erhebt, lässt sich nicht anhand eines objektiven Maßstabs beantworten. Ungleichheit verweist auf kontingente Deutungs- und Interpretationsleistungen, in denen beobachtbare Differenzen nicht nur als Unterschiede behandelt, sondern in Ungleichheiten transformiert werden. Dabei kommt dem Modus der Erzählung eine wesentliche Rolle zu, da er es möglich macht, gesellschaftliche Komplexität auf ein erfassbares Maß zu reduzieren und ambivalente Phänomene zumindest temporär auf eine bestimmte Bedeutung festzulegen. Der vorliegende Beitrag erörtert die Logik und Funktionsweise derartiger erzählerischer Transformationsleistungen anhand der Kategorie der Mittelschicht, die aufgrund ihrer symbolischen Logik bei narrativen Verarbeitungen sozialer Verhältnisse eine besondere Performativität entfaltet. Anhand der bundesdeutschen medialen Öffentlichkeit wird rekonstruiert, in welche Erzählungen „die Mittelschicht“ eingebunden ist und wie hierüber eine kollektiv wirksame symbolische Ordnung von Ungleichheit sowie korrespondierende Vorstellungen über „rationales“ wohlfahrtsstaatliches Regieren etabliert werden. Es werden vier Narrative unterschieden – das Metanarrativ der Mittelschichtsgesellschaft sowie die Narrative der verdienstvollen, der bedrohten und der bevorzugten Mittelschicht –, die ein je eigenes Bild von der Gestalt, den Ursachen, den Auswirkungen und der (Il‑)Legitimität von Ungleichheit zeichnen und in ihrer Gesamtheit ein kollektives Wissen über soziale Unterschiede und deren Regierbarkeit etablieren. Der Beitrag entschlüsselt somit die narrative Vermittlung von Ungleichheit in zweierlei Weise: zum einen als Praxis der Übermittlung von gesellschaftlicher Komplexität in die Sphäre kollektiver Wahrnehmbarkeit und zum anderen als Praxis der Bezugnahme auf Vorstellungen von der gesellschaftlichen Mitte, die als beweglicher Referenzpunkt fungiert, um Ungleichheit von „bloßen“ Differenzen zu unterscheiden.
Wahrgenommene Gruppennormen und ihre Bedeutung für die soziale Akzeptanz und Ablehnung in Grundschulklassen
Authors: Schwalbe Anja , Müller Christoph M. , Wilbert Jürgen 
Published: July 2021

ZusammenfassungNormen definieren Kriterien für die soziale Akzeptanz und Ablehnung von Kindern in einer Klasse. Welche Normen Grundschulkinder jedoch als relevant für die soziale Akzeptanz bzw. Ablehnung wahrnehmen ist unklar. Dieses Desiderat wurde in einer Interviewstudie (N = 38) und darauf aufbauend in einer Fragebogenstudie (N = 647) adressiert. Die Befunde machen auf die Bedeutung des Sozialverhaltens als wahrgenommene Gruppennorm für die Akzeptanz und Ablehnung aufmerksam, die sich über die Klassenstufen hinweg als stabil erwies. Jahrgangsspezifische Unterschiede fanden sich hingegen für die Bedeutung formeller Normen (z. B. mit Bezug zur Schulleistung), die von Kindern in den höheren Klassenstufen als weniger relevant für den sozialen Status wahrgenommen wurden, als von jenen in den unteren Klassenstufen.
Communicating Drivers of Environmental Change Through Transdisciplinary Human‐Environment Modeling
Authors: Allison Andrew E. F. , Dickson Mark E. , Fisher Karen T. , Thrush Simon F. 
Published: July 2021

AbstractA scientific storytelling approach is used to communicate results from a transdisciplinary model of human‐environment estuarine systems for the purpose of developing system understanding and improving transdisciplinary communication. Questionnaires and a media analysis are used to collate public perceptions of observed environmental change in estuarine systems, with an agent‐based model developed to investigate the effects of these environmental changes and the complex network of interactions that lead to them. Five scenarios that correspond to the main public interests identified during questionnaire analyses are presented and described using a narrative textual approach; flow diagrams are used to explain model processes and interactions. We test whether the earth science storytelling approach of Phillips (2012), https://doi.org/10.1016/j.earscirev.2012.09.005 can be applied more broadly to transdisciplinary models of complex human‐environment systems. Results indicate that all eight storytelling plots of Phillips (2012), https://doi.org/10.1016/j.earscirev.2012.09.005 are applicable to describing pathways within human‐environment systems and are useful in succinctly explaining complex interactions within such systems; the crucial initial step is determining what needs to be communicated and subsequently deciding on appropriate plot or plots to convey the story.
A Generalized Interpolation Material Point Method for Shallow Ice Shelves. 1: Shallow Shelf Approximation and Ice Thickness Evolution
Authors: Huth Alex , Duddu Ravindra , Smith Ben 
Published: July 2021

AbstractWe develop a generalized interpolation material point method (GIMPM) for the shallow shelf approximation (SSA) of ice flow. The GIMPM, which can be viewed as a particle version of the finite element method, is used here to solve the shallow shelf approximations of the momentum balance and ice thickness evolution equations. We introduce novel numerical schemes for particle splitting and integration at domain boundaries to accurately simulate the spreading of an ice shelf. The advantages of the proposed GIMPM‐SSA framework include efficient advection of history or internal state variables without diffusion errors, automated tracking of the ice front and grounding line at sub‐element scales, and a weak formulation based on well‐established conventions of the finite element method with minimal additional computational cost. We demonstrate the numerical accuracy and stability of the GIMPM using 1‐D and 2‐D benchmark examples. We also compare the accuracy of the GIMPM with the standard material point method (sMPM) and a reweighted form of the sMPM. We find that the grid‐crossing error is very severe for SSA simulations with the sMPM, whereas the GIMPM successfully mitigates this error. While the grid‐crossing error can be reasonably reduced in the sMPM by implementing a simple material point reweighting scheme, this approach it not as accurate as the GIMPM. Thus, we illustrate that the GIMPM‐SSA framework is viable for the simulation of ice sheet‐shelf evolution and enables boundary tracking and error‐free advection of history or state variables, such as ice thickness or damage.
First Concurrent Observations of NO2 and CO2 From Power Plant Plumes by Airborne Remote Sensing
Authors: Fujinawa Tamaki , Kuze Akihiko , Suto Hiroshi , Shiomi Kei , Kanaya Yugo , Kawashima Takahiro , Kataoka Fumie , Mori Shigetaka , Eskes Henk , Tanimoto Hiroshi 
Published: July 2021

AbstractCombined NO2 and CO2 observations have the potential to constrain the identification of the locations and strength of urban CO2 emissions, in particular, point sources such as power plants. We report the first results of airborne spectroscopic NO2 and CO2 observations over an urban area in Japan in February 2018. Inversed emission rates of two stacks of the coal‐fired power plant for CO2 showed relatively good agreement with those estimated by a bottom‐up inventory—the Regional Emission inventory in ASia (REAS) v3.1—within −7% to 40% because the plume shapes were well identified due to constraint by NO2 measurements. The estimated NOx emission rates showed discrepancies more than 80% with those estimated by the REAS v3.1, mainly due to the uncertainties in activity data and emission factors, or in the greatly varying NO/NO2 ratios in fresh plumes, which warrant further investigations when estimating NOx emissions from satellite NO2 observations on km‐scales.
S100A9 in adult asthmatic patients: a biomarker for neutrophilic asthma
Authors: Quoc Quang Luu , Choi Youngwoo , Thi Bich Tra Cao , Yang Eun-Mi , Shin Yoo Seob , Park Hae-Sim 
Published: July 2021

AbstractThe biomarkers and therapeutic targets of neutrophilic asthma (NA) are poorly understood. Although S100 calcium-binding protein A9 (S100A9) has been shown to correlate with neutrophil activation, its role in asthma pathogenesis has not been clarified. This study investigated the mechanism by which S100A9 is involved in neutrophil activation, neutrophil extracellular trap (NET)-induced airway inflammation, and macrophage polarization in NA. The S100A9 levels (by ELISA) in sera/culture supernatant of peripheral blood neutrophils (PBNs) and M0 macrophages from asthmatic patients were measured and compared to those of healthy controls (HCs). The function of S100A9 was evaluated using airway epithelial cells (AECs) and PBNs/M0 macrophages from asthmatic patients, as well as a mouse asthma model. The serum levels of S100A9 were higher in NA patients than in non-NA patients, and there was a positive correlation between serum S100A9 levels and sputum neutrophil counts (r = 0.340, P = 0.005). Asthmatic patients with higher S100A9 levels had lower PC20 methacholine values and a higher prevalence of severe asthma (SA) (P < .050). PBNs/M0 macrophages from SA released more S100A9 than those from non-SA patients. PBNs from asthmatic patients induced S100A9 production by AECs, which further activated AECs via the extracellular signal-regulated kinase (ERK) pathway, stimulated NET formation, and induced M1 macrophage polarization. Higher S100A9 levels in sera, bronchoalveolar lavage fluid, and lung tissues were observed in the mouse model of NA but not in the other mouse models. These results suggest that S100A9 is a potential serum biomarker and therapeutic target for NA.
SREBP1 site 1 protease inhibitor PF-429242 suppresses renal cell carcinoma cell growth
Authors: Wang Tong-bing , Geng Mei , Jin Hua , Tang Ai-guo , Sun Hao , Zhou Liu-zheng , Chen Bin-hai , Shen Gang , Sun Qiang 
Published: July 2021

AbstractRenal cell carcinoma (RCC) cells have increased lipogenesis and cholesterol synthesis. Sterol regulatory element-binding protein-1 (SREBP1) is cleaved by site 1 protease (S1P) to release the transcriptionally active amino-terminal domain. PF-429242 is a potent and competitive S1P inhibitor. We here tested its activity in RCC cells. In established and primary human RCC cells, PF-429242 potently inhibited cell proliferation, migration, and invasion. The S1P inhibitor provoked apoptosis activation in RCC cells. Furthermore, shRNA-mediated S1P silencing or CRISPR/Cas9-induced S1P knockout led to RCC cell growth inhibition and apoptosis activation. Conversely, ectopic overexpression of SREBP1 or S1P augmented RCC cell proliferation and migration. Daily i.v. injection of a single dose of PF-429242 robustly inhibited RCC xenograft growth in severe combined immunodeficiency mice. Additionally, intratumoral injection of S1P shRNA lentivirus inhibited RCC xenograft growth in mice. SREBP1, S1P, and its target gene low density lipoprotein receptor (LDLR) were significantly elevated in human RCC tissues. These results suggest that targeting S1P by PF-429242 inhibited RCC cell growth in vitro and in vivo.
TGF-β1-mediated exosomal lnc-MMP2-2 increases blood–brain barrier permeability via the miRNA-1207-5p/EPB41L5 axis to promote non-small cell lung cancer brain metastasis
Authors: Wu Dongming , Deng Shihua , Li Li , Liu Teng , Zhang Ting , Li Jing , Yu Ye , Xu Ying 
Published: July 2021

AbstractBrain metastases remain a major problem in patients with advanced non-small cell lung cancer (NSCLC). The permeability of the blood–brain barrier (BBB) is highly increased during lung cancer brain metastasis; however, the underlying mechanism remains largely unknown. We previously found that lnc-MMP2-2 is highly enriched in tumor growth factor (TGF)-β1-mediated exosomes and regulates the migration of lung cancer cells. This study aimed to explore the role of exosomal lnc-MMP2-2 in the regulation of BBB and NSCLC brain metastasis. Here, using endothelial monolayers and mouse models, we found that TGF-β1-mediated NSCLC-derived exosomes efficiently destroyed tight junctions and the integrity of these natural barriers. Overexpression of lnc-MMP2-2 in human brain microvascular endothelial cells increased vascular permeability in endothelial monolayers, whereas inhibition of lnc-MMP2-2 alleviated these effects. Furthermore, lnc-MMP2-2 knockdown markedly reduced NSCLC brain metastasis in vivo. Mechanistically, through luciferase reporter assays, RNA pull-down assay, and Ago2 RNA immunoprecipitation assay, we showed that lnc-MMP2-2 served as a microRNA sponge or a competing endogenous RNA for miR-1207-5p and consequently modulated the derepression of EPB41L5. In conclusion, TGF-β1-mediated exosomal lnc-MMP2-2 increases BBB permeability to promote NSCLC brain metastasis. Thus, exosomal lnc-MMP2-2 may be a potential biomarker and therapeutic target against lung cancer brain metastasis.
Comparable radiation sensitivity in p53 wild-type and p53 deficient tumor cells associated with different cell death modalities
Authors: Li Ping , Liu Xiongxiong , Zhao Ting , Li Feifei , Wang Qiqi , Zhang Pengcheng , Hirayama Ryoichi , Chen Weiqiang , Jin Xiaodong , Zheng Xiaogang , Wang Zhen , Li Qiang 
Published: July 2021

AbstractStudies of radiation interaction with tumor cells often take apoptosis as the desired results. However, mitotic catastrophe and senescence are also promoted by clinically relevant doses of radiation. Furthermore, p53 is a well-known transcription factor that is closely associated with radiosensitivity and radiation-induced cell death. Therefore, we aimed to investigate the involvement of radiosensitivity, cell death modalities and p53 status in response to carbon-ion radiation (CIR) here. Isogenic human colorectal cancer cell lines HCT116 (p53+/+ and p53−/−) were irradiated with high-LET carbon ions. Cell survival was determined by the standard colony-forming assay. 53BP1 foci were visualized to identify the repair kinetics of DNA double-strand breaks (DSBs). Cellular senescence was measured by SA-β-Gal and Ki67 staining. Mitotic catastrophe was determined with DAPI staining. Comparable radiosensitivities of p53+/+ and p53−/− HCT116 colorectal cells induced by CIR were demonstrated, as well as persistent 53BP1 foci indicated DNA repair deficiency in both cell lines. Different degree of premature senescence in isogenic HCT116 colorectal cancer cells suggested that CIR-induced premature senescence was more dependent on p21 but not p53. Sustained upregulation of p21 played multifunctional roles in senescence enhancement and apoptosis inhibition in p53+/+ cells. p21 inhibition further increased radiosensitivity of p53+/+ cells. Complex cell death modalities rather than single cell death were induced in both p53+/+ and p53−/− cells after 5 Gy CIR. Mitotic catastrophe was predominant in p53−/− cells due to inefficient activation of Chk1 and Chk2 phosphorylation in combination with p53 null. Senescence was the major cell death mechanism in p53+/+ cells via p21-dependent pathway. Taken together, p21-mediated premature senescence might be used by tumor cells to escape from CIR-induced cytotoxicity, at least for a time.
A boronate gel-based synthetic platform for closed-loop insulin delivery systems
Authors: Matsumoto Akira , Chen Siyuan 
Published: July 2021

AbstractDiabetes is one of the most devastating global diseases with an ever-increasing number of patients. Achieving persistent glycemic control in a painless and convenient way is an unmet goal for diabetes management. Insulin therapy is commonly utilized for diabetes treatment and usually relies on patient self-injection. This not only impairs a patient’s quality of life and fails to precisely control the blood glucose level but also brings the risk of life-threatening hypoglycemia. “closed-loop” insulin delivery systems could avoid these issues by providing on-demand insulin delivery. However, safety concerns limit the application of currently developed electronics-derived or enzyme-based systems. Phenylboronic acid (PBA), with the ability to reversibly bind glucose and a chemically tailored binding specificity, has attracted substantial attention in recent years. This focus review provides an overview of PBA-based versatile insulin delivery platforms developed in our group, including new PBA derivatives, glucose-responsive gels, and gel-combined medical devices, with a unique “skin layer” controlled diffusion feature.